[109] Quantitative proteome analysis of mouse liver lysosomes provides evidence for mannose 6-phosphate-independent targeting mechanisms of acid hydrolases in mucolipidosis II. Markmann S, Krambeck S, Hughes CJ, Mirzaian M, Aerts JM, Saftig P, Schweizer M, Vissers JC, Braulke T, Damme M (2016) Mol Cell Proteomics pii: mcp.M116.063636 Abstract

[108] Disease-causing mutations affecting surface residues of mitochondrial glutaryl-CoA dehydrogenase impair stability, heteromeric complex formation and mitochondria architecture. Schmiesing J, Lohmöller B, Schweizer M, Tidow H, Gersting SW, Muntau AC, Braulke T, Mühlhausen C (2016) Hum Mol Genet pii: ddw411 Abstract


[107] Identification of the interaction domains between α- and γ-subunits of GlcNAc-1-phosphotransferase. Velho RV, De Pace R, Tidow H, Braulke T, Pohl S (2016) FEBS Lett 23:4287-95 Abstract

[106] Mannose 6-phosphate-dependent targeting of lysosomal enzymes is required for normal craniofacial and dental development. Koehne T, Markmann S, Schweizer M, Muschol N, Friedrich RE, Hagel C, Glatzel M, Kahl-Nieke B, Amling M, Schinke T, Braulke T (2016)Biochim Biophys Acta 1862:1570-80 Abstract

[105] Retinal Degeneration in Mice Deficient in the Lysosomal Membrane Protein CLN7. Jankowiak W, Brandenstein L, Dulz S, Hagel C, Storch S, Bartsch U (2016) Invest Ophthalmol Vis Sci 57:4989-98 Abstract

[104] Single-chain antibody-fragment M6P-1 possesses a mannose 6-phosphate monosaccharide-specific binding pocket that distinguishes N-glycan phosphorylation in a branch-specific manner. Blackler RJ, Evans DW, Smith DF, Cummings RD, Brooks CL, Braulke T, Liu X, Evans SV, Müller-Loennies S (2016) Glycobiology 26:181-92 Abstract

[103] Lysosomal dysfunction and impaired autophagy in a novel mouse model deficient for the lysosomal membrane protein Cln7. Brandenstein L, Schweizer M, Sedlacik J, Fiehler J, Storch S (2016) Hum Mol Genet 25:777-91 Abstract


[102] In Vivo Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11. Varga RE, Khundadze M, Damme M, Nietzsche S, Hoffmann B, Stauber T, Koch N, Hennings JC, Franzka P, Huebner AK, Kessels MM, Biskup C, Jentsch TJ, Qualmann B, Braulke T, Kurth I, Beetz C, Hübner CA (2015) PLoS Genet 11:e1005454 Abstract

[101] Impaired bone remodeling and its correction by combination therapy in a mouse model of mucopolysaccharidosis-I. Kuehn SC, Koehne T, Cornils K, Markmann S, Riedel C, Pestka JM, Schweizer M, Baldauf C, Yorgan TA, Krause M, Keller J, Neven M, Breyer S, Stuecker R, Muschol N, Busse B, Braulke T, Fehse B, Amling M, Schinke T (2015) Hum Mol Genet 24:7075-86 Abstract

[100] Mannose 6 phosphorylation of lysosomal enzymes controls B cell function. Otomo T, Schweizer M, Kollmann K, Schumacher V, Muschol N, Tolosa E, Mittrücker HW, Braulke T (2015) J Cell Biol 208:171-80 Abstract

[99] Lrp1/LDL Receptor Play Critical Roles in Mannose 6-Phosphate-Independent Lysosomal Enzyme Targeting. Markmann S, Thelen M, Cornils K, Schweizer M, Brocke-Ahmadinejad N, Willnow T, Heeren J, Gieselmann V, Braulke T, Kollmann K (2015) Traffic 16:743-59 Abstract

[98] Analyses of disease-related GNPTAB mutations define a novel GlcNAc1-phosphotransferase interaction domain and an alternative site-1 protease cleavage site. Velho RV, De Pace R, Klünder S, Sperb-Ludwig F, Lourenço CM, Schwartz IV, Braulke T, Pohl S (2015) Hum Mol Genet 24:3497-505 Abstract

[97] Sustained Neural Stem Cell-Based Intraocular Delivery of CNTF Attenuates Photoreceptor Loss in the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis. Jankowiak W, Kruszewski K, Flachsbarth K, Skevas C, Richard G, Rüther K, Braulke T, Bartsch U (2015) PLoS One 10:e0127204 Abstract

[96] Lysoplex: An efficient toolkit to detect DNA sequence variations in the autophagy-lysosomal pathway. Di Fruscio G, Schulz A, De Cegli R, Savarese M, Mutarelli M, Parenti G, Banfi S, Braulke T, Nigro V, Ballabio A (2015) Autophagy 11:928-38 Abstract

[95] Site-1 protease-activated formation of lysosomal targeting motifs is independent of the lipogenic transcription control. Klünder S, Heeren J, Markmann S, Santer R, Braulke T, Pohl S (2015) J Lipid Res 56:1625-32 Abstract

[94] Mannose 6-phosphate-independent Lysosomal Sorting of LIMP-2. Blanz J, Zunke F, Markmann S, Damme M, Braulke T, Saftig P, Schwake M (2015) Traffic 16:1127-36 Abstract

[93] Subunit interactions of the disease-related hexameric GlcNAc-1-phosphotransferase complex. De Pace R, Velho RV, Encarnação M, Marschner K, Braulke T, Pohl S (2015) Hum Mol Genet 24:6826-35 Abstract

[92] Impaired bone remodeling and its correction by combination therapy in a mouse model of mucopolysaccharidosis-I. Kuehn SC, Koehne T, Cornils K, Markmann S, Riedel C, Pestka JM, Schweizer M, Baldauf C, Yorgan TA, Krause M, Keller J, Neven M, Breyer S, Stuecker R, Muschol N, Busse B, Braulke T, Fehse B, Amling M, Schinke T (2015) Hum Mol Genet 24:7075-86 Abstract

[91] Biosynthesis, targeting, and processing of lysosomal proteins: pulse-chase labeling and immune precipitation. Pohl S, Hasilik A (2015) Methods Cell Biol 126:63-83 Abstract


[90] Molecular characterization of arylsulfatase G: expression, processing, glycosylation, transport, and activity. Kowalewski B, Lübke T, Kollmann K, Braulke T, Reinheckel T, Dierks T, Damme M (2014) J Biol Chem 289:27992-8005 Abstract

[89] Lysine glutarylation is a protein posttranslational modification regulated by SIRT5.
Tan M, Peng C, Anderson KA, Chhoy P, Xie Z, Dai L, Park J, Chen Y, Huang H, Zhang Y, Ro J, Wagner GR, Green MF, Madsen AS, Schmiesing J, Peterson BS, Xu G, Ilkayeva OR, Muehlbauer MJ, Braulke T, Mühlhausen C, Backos DS, Olsen CA, McGuire PJ, Pletcher SD, Lombard DB, Hirschey MD, Zhao Y (2014) Cell Metab 19:605-17 Abstract

[88] Mucolipidosis II-Related Mutations Inhibit the Exit from the Endoplasmic Reticulum and Proteolytic Cleavage of GlcNAc-1-Phosphotransferase Precursor Protein (GNPTAB). De Pace R, Coutinho MF, Koch-Nolte F, Haag F, Prata MJ, Alves S, Braulke T, Pohl S (2014) Hum Mutat 35:368-76 Abstract

[87] Interaction of Glutaric Aciduria Type 1-Related glutaryl-CoA Dehydrogenase with Mitochondrial Matrix Proteins. Schmiesing J, Schlüter H, Ullrich K, Braulke T, Mühlhausen C (2014) PLoS One 9:e87715 Abstract

[86] Gene disruption of Mfsd8 in mice provides the first animal model for CLN7 disease. Damme M, Brandenstein L, Fehr S, Jankowiak W, Bartsch U, Schweizer M, Hermans- Borgmeyer I, Storch S (2014) Neurobiol Dis 65C:12-24 Abstract


[85] A hereditary spastic paraplegia mouse model supports a role of ZFYVE26/SPASTIZIN for the endolysosomal system. Khundadze M, Kollmann K, Koch N, Biskup C, Nietzsche S, Zimmer G, Hennings JC, Huebner AK, Symmank J, Jahic A, Ilina EI, Karle K, Schöls L, Kessels M, Braulke T, Qualmann B, Kurth I, Beetz C, Hübner CA (2013) PLoS Genet 9:e1003988 Abstract

[84] Decreased bone formation and increased osteoclastogenesis cause bone loss in mucolipidosis II. Kollmann K, Pestka JM, Kühn SC, Schöne E, Schweizer M, Karkmann K, Otomo T, Catala-Lehnen P, Failla AV, Marshall RP, Krause M, Santer R, Amling M, Braulke T, Schinke T (2013) EMBO Mol Med 5:1871-86 Abstract

[83] Apoptotic Photoreceptor Loss and Altered Expression of Lysosomal Proteins in the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis. Bartsch U, Galliciotti G, Jofre GF, Jankowiak W, Hagel C, Braulke T (2013) Invest Ophthalmol Vis Sci 54:6952-9 Abstract

[82] Ultrastructural analysis of neuronal and non-neuronal lysosomal storage in mucolipidosis type II knock-in mice. Schweizer M, Markmann S, Braulke T, Kollmann K (2013) Ultrastruct Pathol 37:366-72 Abstract

[81] Evaluation of butyrate induced production of a mannose-6-phosphorylated therapeutic enzyme using parallel bioreactors. Madhavarao CN, Agarabi CD, Wong L, Müller-Loennies S, Braulke T, Khan M, Anderson H, Johnson GR (2013) Biotechnol Appl Biochem doi:10.1002/bab.1151 Abstract

[80] Acute renal proximal tubule alterations during induced metabolic crises in a mouse model of glutaric aciduria type 1. Thies B, Meyer-Schwesinger C, Lamp J, Schweizer M, Koeller DM, Ullrich K, Braulke T, Mühlhausen C (2013) Biochim Biophys Acta 1832:1463-72 Abstract

[79] Cell biology and function of neuronal ceroid lipofuscinosis-related proteins. Kollmann K, Uusi-Rauva K, Scifo E, Tyynelä J, Jalanko A, Braulke T (2013) Biochim Biophys Acta 1832:1866-81 Abstract

[78] Mass spectrometric analysis of neutral and anionic N-glycans from a Dictyostelium discoideum model for human congenital disorder of glycosylation CDG IL. Hykollari A, Balog CI, Rendic D, Braulke T, Wilson IB, Paschinger K (2013) J Proteome Res 12:1173-87 Abstract

[77] Transport of the GlcNAc-1-phosphotransferase α/β-subunit precursor protein to the Golgi apparatus requires a combinatorial sorting motif. Franke M, Braulke T, Storch S (2013) J Biol Chem 288:1238-49 Abstract


[76] Lysosomal dysfunction causes neurodegeneration in mucolipidosis II ‘knock-in’ mice. Kollmann K, Damme M, Markmann S, Morelle W, Schweizer M, Hermans-Borgmeyer I, Röchert AK, Pohl S, Lübke T, Michalski JC, Käkelä R. Walkley SU, Braulke T (2012) Brain 135:2661-75 Abstract

[75] The 5-phosphatase OCRL mediates retrograde transport of the mannose 6-phosphate receptor by regulating a Rac1-cofilin signalling module. van Rahden VA, Brand K, Najm J, Heeren J, Pfeffer SR, Braulke T, Kutsche K (2012) Brain 135:2661-75 Abstract

[74] Disruption of the Autophagy-Lysosome Pathway Is Involved in Neuropathology of the nclf Mouse Model of Neuronal Ceroid Lipofuscinosis. Thelen M, Damme M, Schweizer M, Hagel C, Wong AM, Cooper JD, Braulke T, Galliciotti G (2012) Plos One 7:e35493 Abstract

[73] Proteolytic cleavage of the disease-related lysosomal membrane glycoprotein CLN7. Steenhuis P, Froemming J, Reinheckel T, Storch S (2012) Biochem Biophhys Acta 1822:1617-28 Abstract

[72] A novel mannose 6-phosphate specific antibody fragment for diagnosis of Mucolipidosis type II and III. (Book chapter) Pohl S, Braulke T, Müller-Loennies S (2012) In: Anticarbohydrate antibodies - From molecular basis to clinical application (Eds: P. Kosma, S. Müller-Loennies), Springer-Verlag, Wien, 307-327

[71] Multiple Enzyme Deficiencies: Defects in transport: Mucolipidosis II alpha/beta; mucolipidosis III alpha/beta and mucolipidosis III gamma. (Book chapter) Raas-Rothschild A, Pohl S, Braulke T (2012) In: Lysosomal Storage Diseases: A Practical Guide (Eds. A. B. Mehta, B. Winchester), WILEY-BLACKWELL, Oxford

[70] Mannose 6-dephosphorylation of lysosomal proteins mediated by acid phosphatases Acp2 and Acp5. Makrypidi G, Damme M, Müller-Loennies S, Trusch M, Schmidt B, Schlüter H, Heeren J, Lübke T, Saftig P, Braulke T (2012) Mol Cell Biol 32:774-82 Abstract

[69] High expression of disease-related Cln6 in the cerebral cortex, purkinje cells, dentate gyrus, and hippocampal ca1 neurons. Thelen M, Fehr S, Schweizer M, Braulke T, Galliciotti G (2012) J Neurosci Res 90:568-74 Abstract


[68] A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolism. Marschner K, Kollmann K, Schweizer M, Braulke T, Pohl S (2011) Science 333:87-90 Abstract

[67] N-glycans and glycosylphosphatidylinositol-anchor act on polarized sorting of mouse PrP(C) in Madin-Darby canine kidney cells. Puig B, Altmeppen HC, Thurm D, Geissen M, Conrad C, Braulke T, Glatzel M (2011) PLoS One 6:e24624 Abstract

[66] Analysis of Potential Biomarkers and Modifier Genes Affecting the Clinical Course of CLN3 Disease. Lebrun AH, Moll-Khosrawi P, Pohl S, Makrypidi G, Storch S, Kilian D, Streichert T, Otto B, Mole SE, Ullrich K, Cotman S, Kohlschütter A, Braulke T, Schulz A (2011) ) Mol Med 17:1253-61 Abstract

[65] Glutaric aciduria type 1 metabolites impair the succinate transport from astrocytic to neuronal cells. Lamp J, Keyser B, Koeller DM, Ullrich K, Braulke T, Mühlhausen C (2011) J Biol Chem 286:17777-84 Abstract

[64] Residual activity and proteasomal degradation of p.Ser298Pro sulfamidase identified in patients with a mild clinical phenotype of Sanfilippo A syndrome. Muschol N, Pohl S, Meyer A, Gal A, Ullrich K, Braulke T (2011) Am J Med Genet A 155:1634-9 Abstract

[63] Post-translational modifications of the gamma-subunit affect intracellular trafficking and complex assembly of GlcNAc-1-phosphotransferase. Encarnação M, Kollmann K, Trusch M, Braulke T, Pohl S (2011) J Biol Chem 286:5311-8 Abstract


[62] Lysosomal targeting of the CLN7 membrane glycoprotein and transport via the plasma membrane require a dileucine motif. Steenhuis P, Herder S, Gelis S, Braulke T, Storch S (2010) Traffic 11:987-1000 Abstract

[61] A novel single-chain antibody fragment for detection of mannose 6-phosphate-containing proteins. Application in mucolipidosis type II patinets and mice. Müller-Loennies S, Galliciotti G, Kollmann K, Glatzel M, Braulke T (2010) Am J Pathol 177:240-7 Abstract

[60] Proteolytic processing of the gamma-subunit is associated with the failure to form GlcNAc-1-phosphotransferase complexes and mannose 6-phosphate residues on lysosomal enzymes in human macrophages. Pohl S, Tiede S, Marschner K, Encarnação M, Castrichini M, Kollmann K, Muschol N, Ullrich K, Müller-Loennie S, Braulke T (2010) J Biol Chem 285:23936-44 Abstract

[59] Mannose phosphorylation in health and disease. (Review) Kollmann K, Pohl S, Marschner K, Encarnação M, Sakwa I, TiedeS, Poorthuis BJ, Lübke T, Müller-Loennies S, Storch S, Braulke T (2010) Eur J Cell BIol 89:117-23 Abstract

[58] Site specific analysis of N-linked oligosaccharides of recombinant lysosomal arylsulfatase A produced in different cell lines. Schröder S, Matthes F, Hyden P, Andersson C, Fogh J, Müller-Loennies S, Braulke T, Gieselmann V, Matzner U (2010) Glycobiology 20:248-59 Abstract

[57] Loss of N-acetylglucosamine-1-phosphotransferase gamma-subunit due to intronic mutation in GNPTG causes mucolipidosis type III gamma: Implications for molecular and cellular diagnostics. Pohl S, Encarnacão M, Castrichini M, Müller-Loennies S, Muschol N, Braulke T (2010) Am J Med Genet A 152:124-32 Abstract

[56] Pathogenic mutations cause rapid degradation of lysosomal storage disease-related membrane protein CLN6. Kurze AK, Galliciotti G, Heine C, Mole SE, Quitsch A, Braulke T (2010) Hum Mutat 31:E1163-74 Abstract

[55] Glycostructures in biological systems - synthesis and function. (Review) Thiem J, Braulke T (2010) Eur J Cell Biol 89:1 Abstract

[54] Protein kinase a dependent phosphorylation of apical membrane antigen 1 plays an important role in erythrocyte invasion by the malaria parasite. Leykauf K, Treeck M, Gilson PR, Nebl T, Braulke T, Cowman AF, Gilberger TW, Crabb BS (2010) PLoS Pathog 6:e1000941 Abstract


[53] Compensatory expression of human N-acetylglucosaminyl-1 phosphotransferase subunits in mucolipidosis type III gamma. Pohl S, Tiede S, Castrichini M, Cantz M, Gieselmann V, Braulke T (2009) Biochim Biophys Acta 1792:221-5 Abstract

[52] Glycosylation- and phosphorylation-dependent intracellular transport of lysosomal hydrolases. (Review) Pohl S, Marschner K, Storch S, Braulke T (2009) Biol Chem 390:521-7 Abstract

[51] Retention of lysosomal protein CLN5 in the endoplasmic reticulum causes neuronal ceroid lipofuscinosis in Asian sibship. Lebrun AH, Storch S, Rüschendorf F, Schmiedt ML, Kyttälä A, Mole SE, Kitzmüller C, Saar K, Mewasingh LD, Boda V, Kohlschütter A, Ullrich K, Braulke T, Schulz A (2009) Hum Mutat 30:E651-61 Abstract

[50] Lysosomes. (Review) Gieselmann V, Braulke T (2009) Biochim Biophys Acta 1793:603-4 Abstract

[49] Mannose 6-phosphate receptor-dependent endocytosis of lysosomal enzymes is increased in sulfatide-storing kidney cells. Klein D, Yaghootfam A, Matzner U, Koch B, Braulke T, Gieselmann V (2009) Biol Chem 390:41-8 Abstract

[48] Sorting of lysosomal proteins. (Review) Braulke T, Bonifacino JS (2009) Biochim Biophys Acta 1793:605-14 Abstract

[47] Neuronal ceroid lipofuscinoses. (Review) Jalanko A, Braulke T (2009) Biochim Biophys Acta 1793:697-709 Abstract

[46] Identification and molecular characterization of six novel mutations in the UDP-N-acetylglucosamine-1-phosphotransferase gamma subunit (GNPTG) gene in patients with mucolipidosis III gamma. Persichetti E, Chuzhanova NA, Dardis A, Tappino B, Pohl S, Thomas NS, Rosano C, Balducci C, Paciotti S, Dominissini S, Montalvo AL, Sibilio M, Parini R, Rigoldi M, Di Rocco M, Parenti G, Orlacchio A, Bembi B, Cooper DN, Filocamo M, Beccari T (2009) Hum Mutat 30:978-84 Abstract


[45] Molecular order in mucolipidosis II and III nomenclature. Cathey SS, Kudo M, Tiede S, Raas-Rothschild A, Braulke T, Beck M, Taylor HA, Canfield WM, Leroy JG, Neufeld EF, McKusick VA (2008) Am J Med Genet A 146:512-3 Abstract

[44] Transport and distribution of 3-hydroxyglutaric acid before and during induced encephalopathic crises in a mouse model of glutaric aciduria type 1. Keyser B, Glatzel M, Stellmer F, Kortmann B, Lukacs Z, Kölker S, Sauer SW, Muschol N, Herdering W, Thiem J, Goodman SI, Koeller DM, Ullrich K, Braulke T, Mühlhausen C (2008) Biochem Biophys Acta 1782:385-90 Abstract

[43] Organic anion transporters OAT1 and OAT4 mediate the high affinity transport of glutarate derivatives accumulating in patients with glutaric acidurias. Hagos Y, Krick W, Braulke T, Mühlhausen C, Burckhardt G, Burckhardt BC (2008) Pflugers Arch 457:223-31 Abstract

[42] Membrane translocation of glutaric acid and its derivatives. Mühlhausen C, Burckhardt BC, Hagos Y, Burckhardt G, Keyser B, Lukacs Z, Ullrich K, Braulke T (2008) J Inherit Metab Dis 31:188-193 Abstract

[41] The mutation p.Ser298Pro in the sulphamidase gene (SGSH) is associated with a slowly progressive clinical phenotype in mucopolysaccharidosis type IIIA (Sanfilippo A syndrome). Meyer A, Kossow K, Gal A, Steglich C, Mühlhausen C, Ullrich K, Braulke T, Muschol N Meyer A, Kossow K, Gal A, Steglich C, Mühlhausen C, Ullrich K, Braulke T, Muschol (2008) Hum Mut 29:770 Abstract

[40] Molecular analysis of the GlcNac-1-phosphotransferase. (Review) Braulke T, Pohl S, Storch S (2008) J Inherit Metab Dis 31:253-7 Abstract

[39] Accumulation of bis(monoacylglycero)phosphate and gangliosides in mouse models of neuronal ceroid lipofuscinosis. Jabs S, Quitsch A, Käkelä R, Koch B, Tyynelä J, Brade H, Glatzel M, Walkley S, Saftig P, Vanier MT, Braulke T (2008) J Neurochem 106:1414-25 Abstract

[38] Disease-causing missense mutations affect enzymatic activity, stability and oligomerization of glutaryl-CoA dehydrogenase (GCDH). Keyser B, Mühlhausen C, Dickmanns A, Christensen E, Muschol N, Ullrich K, Braulke T (2008) Hum Mol Genet 17:3854-63 Abstract

[37] Multiple post-translational modifications of mouse insulin-like growth factor binding protein-6 expressed in epithelial Madin-Darby canine kidney cells. Shalamanova L, Kübler B, Storch S, Scharf JG, Braulke T (2008) Mol Cell Endocrinol 295:18-23 Abstract


[36] Topology and endoplasmic reticulum retention signals of the lysosomal storage disease-related membrane protein CLN6. Heine C, Quitsch A, Storch S, Martin Y, Lonka L, Lehesjoki AE, Mole S, Braulke T (2007) Mol Membr Biol 24:74-87 Abstract

[35] C-terminal prenylation of the CLN3 membrane glycoprotein is required for efficient endosomal sorting to lysosomes. Storch S, Pohl S, Quitsch A, Falley K, Braulke T (2007) Traffic 8:431-44 Abstract

[34] 3-Hydroxyglutaric acid is transported via the sodium-dependent dicarboxylate transporter NaDC-3. Stellmer F, Keyser B, Burckhardt BC, Koepsell H, Streichert S, Glatzel M, Jabs S, Thiem J, Herdering W, Koeller DM, Goodman SI, Lukacs Z, Ullrich K, Burckhardt G, Braulke T, Mühlhausen C (2007) J Mol Med 85:763-70 Abstract

[33] Alteration of the insulin-like growth factor axis during in vitro differentiation of the human osteosarcoma cell line HOS 58. Viereck V, Siggelkow H, Pannem R, Braulke T, Scharf JG, Kübler B (2007) J Cell Biochem 102:28-40 Abstract

[32] Scoring evaluation of the natural course of mucopolysaccharidosis type IIIA (Sanfilippo Syndorme type A). Meyer A, Kossow K, Gal A, Mühlhausen C, Ullrich K, Braulke T, Muschol N (2007) Pediatrics 120:1255-61 Abstract

[31] Increased expression of lysosomal acid phosphatase (LAP/Acp2) in CLN3-defective cells and mouse brain tissue. Pohl S, Mitchison HM, Kohlschütter A, van Diggelen, O, Braulke T, Storch S (2007) J Neurochem 103:2177-88 Abstract


[30] Endothelial effects of 3-hydroxyglutaric acid: implications for glutaric aciduria type I. Mühlhausen C, Ott N, Chalajour F, Tilki D, Freudenberg F, Ullrich K, Braulke T, Ergün S (2006) Pediatr Res 59:196-202 Abstract

[29] In vitro sulfation of N-acetyllactosaminide by soluble recombinant human beta-Gal-3'- sulfotransferase. Greimel P, Jabs S, Storch S, Cherif S, Honke K, Braulke T, Thiem J (2006) Carbohydr Res 341:918-24 Abstract

[28] Missense Mutation in N-acetylglucosamine-1-phosphotransferase GNPTA gene in a patient with mucolipidosis II induces changes in the size and cellular distribution of GNPTG. Tiede S, Cantz M, Spranger J, Braulke T (2006) Hum Mutat 27:830-6 Abstract

[27] Functional Biology of the Neuronal Ceroid Lipofuscinoses (NCL) proteins. (Review) Kyttälä A, Lahtinen U, Braulke T, Hofmann SL (2006) Biochim Biophys Acta 1762:920-33 Abstract


[26] Transport of lysosomal enzymes. (Book chapter) Storch S, Braulke T (2005) In: Lysosomes (P. Saftig, ed) Georgetown: Landes Bioscience: Springer Science+Business Media, New York, pp 17-26

[25] Interaction of IGF-II with multiple plasma proteins. High-affinity binding of plasminogen to IGF-ll and IGF-binding protein-3. Oesterreicher S, Blum WF, Schmidt B, Braulke T, Kübler B (2005) J Biol Chem 280:9994-10000 Abstract

[24] Diversity of human insulin-like growth factor (IGF) binding protein-2 fragments in plasma: primary structure, IGF-binding properties, and disulfide bonding pattern. Mark S, Kübler B, Höning S, Oesterreicher S, John H, Braulke T, Forssmann WG, Ständker L (2005) Biochemistry 44:3644-52 Abstract

[23] Missense mutations in the N-acetylglucosamine-1-phosphotransferase a/b subunit gene in a patient with mucolipidosis III and a mild clinical phenotype. Tiede S, Muschol N, Reutter G, Cantz M, Ullrich K, Braulke T (2005) Am J Med Gen A 137:235-40 Abstract

[22] Mucolipidosis II is caused by mutations in MGC4170 gene encoding the alpha/beta GlcNac-1-phosphotransferase. Tiede S, Storch S, Lübke T, Henrissat B, Raas-Rothschild A, Braulke T (2005) Nature Med 11:1109-12 Abstract


[21] Transport, enzymatic activity and stability of mutant sulfamidase (SGSH) identified in patients with Mucopolysaccharidosis type IIIA. Muschol N, Storch S, Ballhausen D, Beesley C, Westermann JC, Gal A, Ullrich K, Hopwood JJ, Winchester B, Braulke T (2004) Hum Mutat 23:559-66 Abstract

[20] Mutation of the glycosylated asparagine residue 286 in human CLN2 protein results in loss of enzymatic activity. Tsiakas K, Steinfeld R, Storch S, Ezaki J, Lucaz Z, Kohlschütter A, Kominami E, Ullrich K, Braulke T (2004) Glycobiology 14:1C-5C Abstract

[19] IGF-binding protein-3 fragments in plasma of a child with acute renal failure. Schebeck-Fürstenberg V, Ständker L, Oppermann M, Müller-Wiefel DE, Blum WF, Braulke T, Kübler B (2004) Ped Nephrol 19:1418-25 Abstract

[18] Vascular dysfunction as an additional pathomechanism in glutaric aciduria type I. Mühlhausen C, Ergün S, Strauss K, Koeller D, Crnic L, Woontner M, Goodman SI, Ullrich K, Braulke T (2004) J Inherit Metab Dis 27:829-34 Abstract

[17] Defective ER-resident membrane protein CLN6 affects lysosomal degradation of endocytosed arylsulfatase A. Heine C, Koch B, Storch S, Kohlschütter A, Palmer DN, Braulke T (2004) J Biol Chem 279:22347-52 Abstract

[16] Mono-allelic expression of the IGF I receptor does not affect IGF responses in human fibroblasts. Hammer E, Kutsche K, Haag F, Ullrich K, Willig RP, Braulke T, Kübler B (2004) Europ J Endocrinol 151:521-9 Abstract

[15] Insulin-like growth factor binding protein-1 is highly induced during acute carbon tetrachloride liver injury and potentiates the IGF-I-stimulated activation of rat hepatic stellate cells. Scharf JG, Dombrowski F, Novosyadlyy R, Eisenbach C, Demori I, Kübler B. Braulke T (2004) Endocrinology 145:3463-72 Abstract

[14] A dileucine motif and a cluster of acidic amino acids in the second cytoplasmic domain of the Batten disease-related CLN3 Protein are required for efficient lysosomal targeting. Storch S, Pohl S, Braulke T (2004) J Biol Chem 279:53625-34 Abstract

[13] A novel mutation in UDP-N-acetylglucosamine-1-phosphotransferase gamma subunit (GNPTAG) in two siblings with mucolipidosis type III alters a used glycosylation site. Tiede S, Cantz M, Raas-Rothschild A, Muschol N, Bürger F, Ullrich K, Braulke T (2004) Hum Mutat 24:535 Abstract


[12] A new type of congenital disorders of glycosylation (CDG-Ii) provides new insights into the early steps of dolichol-linked oligosaccharides biosynthesis. Thiel C, Schwarz M, Peng J, Grzmil M, Hasilik M, Braulke T, Kohlschütter A, von Figura K, Lehle L, Körner C (2003) J Biol Chem 278:22498-505 Abstract

[11] A replacement of the active-site aspartic acid residue 293 in mouse cathepsin D affects its intracellular stability, processing and transport in HEK-293 cells. Partanen S, Storch S, Löffler HG, Hasilik A, Tyynelä J, Braulke T (2003) Biochem J 369:55-62 Abstract

[10] Mutational analysis in longest known survivor of mucopolysaccharidosis type VII. Storch S, Wittenstein B, Islam R, Ullrich K, Sly WS, Braulke T (2003) Hum Genet 112:190-4 Abstract

[09] The role of the IGF axis in hepatocarcinogenesis.Scharf JG, Braulke T (2003) Horm Metab Res 35:685-93 Abstract

[08] In vivo processed fragments of IGF binding protein-2 copurified with bioactive IGF-II. Ständker L, Kübler B, Obendorf M, Braulke T, Forssmann WG, Mark S (2003) Biochie Biophys Res Commun 304:708-13 Abstract

[07] Enhanced expression of manganese-dependent superoxide dismutase in human and sheep CLN6 tissues. Heine C, Tyynelä J, Cooper JD, Palmer DN, Elleder M, Kohlschütter A, Braulke T (2003) Biochem J 376:369-76 Abstract


[06] Secretion of phosphomannosyl-deficient arylsulphatase A and cathepsin D from isolated human macrophages. Muschol N, Matzner U, Tiede S, Gieselmann V, Ullrich K, Braulke T (2002) Biochem J 368:845-53 Abstract

[05] Isolation and characterization of circulating fragments of the insulin-like growth factor binding protein-3. Kübler B, Draeger C, John H, Andag U, Scharf JG, Forssmann WG, Braulke T, Ständker L (2002) FEBS Lett 518:124-8 Abstract

[04] Decreased intracellular degradation of insulin-like growth factor binding protein-3 in cathepsin L-deficient fibroblasts. Zwad O, Kübler B, Roth W, Scharf JG, Saftig P, Peters C, Braulke T (2002) FEBS Lett 510:211-5 Abstract


[03] Multiple C-terminal motifs of the 46-kDa mannose 6-phosphate receptor tail contribute to efficient binding of medium chains of AP-2 and AP-3. Storch S, Braulke T (2001) J Biol Chem 276:4298-303 Abstract

[02] MDCK cells secrete neutral proteases cleaving insulin-like growth factor binding protein-2 to -6. Shalamanova L, Kübler B, Scharf JG, Wewer U, Braulke T (2001) Am J Physiol Endocrinol Metab 281:E1221-9 Abstract

[01] Transferrin binds insulin-like growth factors and affects binding properties of insulin-like growth factor binding protein-3. Storch S, Kübler B, Höning S, Ackmann M, Zapf J, Blum W, Braulke T (2001) FEBS Lett 509:395-8 Abstract

UKE Paper of the Month

  • März 2015
  • März 2015

    UKE Paper of the Month March 2015

    Mannose 6 phosphorylation of lysosomal enzymes controls B cell functions
    Takanobu Otomo, Michaela Schweizer, Katrin Kollmann, Valéa Schumacher, Nicole Muschol, Eva Tolosa, Hans-Willi Mittrücker, Thomas Braulke

    The Journal of Cell Biology 2015, 208:171-80

    ABSTRACT: Antigen processing and presentation and cytotoxic targeting depend on the activities of several lysosomal enzymes which require mannose 6-phosphate (M6P) sorting signals for efficient intracellular transport and localization. In this paper, we show that mice deficient in the formation of M6P residues exhibit significant loss of cathepsin proteases in B cells, leading to lysosomal dysfunction with accumulation of storage material, impaired antigen processing and presentation, and subsequent defects in B cell maturation and antibody production. The targeting of lysosomal and granular enzymes lacking M6P residues is less affected in dendritic cells and T cells and sufficient for maintenance of degradative and lytic functions. M6P deficiency also impairs serum immunoglobulin levels and antibody responses to vaccination in patients. Our data demonstrate the critical role of M6P-dependent transport routes for B cell functions in vivo and humoral immunity in mice and human.

    STATEMENT: Mucolipidosis II (MLII) is a severe inherited lysosomal storage disorder in children affecting several organs. The disease is caused by the incapability to modify 60 lysosomal enzymes with mannose 6-phosphate (M6P) residues which subsequently leads to missorting and hypersecretion of multiple enzymes associated with lysosomal dysfunction and accumulation of nondegraded storage material. However, depending on the cell type the targeting efficiency varies for selected lysosomal enzymes. In the present study, we demonstrated for the first time that in B cells of an MLII mouse model, lysosomal cathepsin proteases were severely decreased and impair proliferation, differentiation, proteolytic antigen processing and interactions with T helper cells, resulting in reduced antibody response. In contrast, the functions of other immune cells were only moderately affected. Importantly, defective humoral immunity was also observed in MLII patients suggesting that the functionally impaired immune system contributes to the high predisposition to infections in MLII patients.

    BACKGROUND: This work was performed as an interdisciplinary project at the Dept. of Immunology and Dept. of Biochemistry, Children´s Hospital in the group of Hans-Willi Mittrücker and Thomas Braulke, respectively, in collaboration with Michaela Schweizer of the Center for Molecular Neurobiology. Takanobu Otomo received a 2-yrs Postdoctoral Fellowship by the Japan Society for the Promotion of Science. This study was supported by the DFG (FOR885, MI 476/3, SFB841 and KFO228), and the Thyssen Foundation. Thomas Braulke's group is interested in the biogenesis and function of lysosomes, and inherited lysosomal storage diseases.

  • UKE Paper of the Month September 2012

    Lysosomal dysfunction causes neurodegeneration in mucolipidosis II 'knock-in' mice
    Katrin Kollmann, Markus Damme, Sandra Markmann, Willy Morelle, Michaela Schweizer, Irm Hermans-Borgmeyer, Anna Katharina Röchert, Sandra Pohl, Torben Lübke, Jean-Claude Michalski, Reijo Käkelä, Steven U Walkley, Thomas Braulke

    Brain 2012, 135:2661-75 (PMID: 22961545)

    ABSTRACT: Mucolipidosis II is a neurometabolic lysosomal trafficking disorder of infancy caused by loss of mannose 6-phosphate targeting signals on lysosomal proteins, leading to lysosomal dysfunction and accumulation of non-degraded material. However, the identity of storage material and mechanisms of neurodegeneration in mucolipidosis II are unknown. We have generated 'knock-in' mice with a common mucolipidosis II patient mutation that show growth retardation, progressive brain atrophy, skeletal abnormalities, elevated lysosomal enzyme activities in serum, lysosomal storage in fibroblasts and brain and premature death, closely mimicking the mucolipidosis II disease in humans. The examination of affected mouse brains at different ages by immunohistochemistry, ultrastructural analysis, immunoblotting and mass spectrometric analyses of glycans and anionic lipids revealed that the expression and proteolytic processing of distinct lysosomal proteins such as a-L-fucosidase, b-hexosaminidase, a-mannosidase or Niemann-Pick C2 protein are more significantly impacted by the loss of mannose 6-phosphate residues than enzymes reaching lysosomes independently of this targeting mechanism. As a consequence, fucosylated N-glycans, GM2 and GM3 gangliosides, cholesterol and bis(monoacylglycero)phosphate accumulate progressively in the brain of mucolipidosis II mice. Prominent astrogliosis and the accumulation of organelles and storage material in focally swollen axons were observed in the cerebellum and were accompanied by a loss of Purkinje cells. Moreover, an increased neuronal level of the microtubule-associated protein 1 light chain 3 and the formation of p62-positive neuronal aggregates indicate an impairment of constitutive autophagy in the mucolipidosis II brain. Our findings demonstrate the essential role of mannose 6-phosphate for selected lysosomal proteins to maintain the capability for degradation of sequestered components in lysosomes and autophagolysosomes and prevent neurodegeneration. These lysosomal proteins might be a potential target for a valid therapeutic approach for mucolipidosis II disease.

    STATEMENT: "This paper report on the generation of a knock-in mouse which shows all symptoms of the human lysosomal storage disorder mucolipidosis II. This comprehensive and interdisciplinary study allowed i) to follow the progression and region-specific neurodegeneration in the disease, ii) the characterization of impaired constitutive autophagy as pathogenic mechanism for neuronal cell death, iii) the identification of storage material using lipidomics and glycomics, and iv) to define subpopulations of lysosomal enzymes that are more susceptible to the loss of mannose 6-phosphate residues than others and therefore more crucial for lysosome functions in the brain. These enzymes represent potential targets for specific enzyme replacement or alternative therapies. Finally, the data provide insight into sequential degradative processes which may be applicable to other lysosomal disorders."

    BACKGROUND: This work was performed at the Department of Biochemistry at the Children's Hospital in the group of Thomas Braulke in collaboration with Michaela Schweizer and Irm Hermans-Borgmeyer of the Center for Molecular Neurobiology. The study was supervised by Dr. Katrin Kollmann and comprises parts of the PhD thesis of Sandra Markmann (MSc) and MD thesis of Anna Katharina Röchert, associated and graduated members of the DFG-funded Research Training Group "Sorting and Interactions between Proteins of Subcellular compartments" (GRK1459). The Braulke group is interested in inherited metabolic and neurodegenerative diseases, and in the biogenesis and functions of the lysosomal compartment.

  • UKE Paper of the Month August 2012

    The 5-phosphatase OCRL mediates retrograde transport of the mannose 6-phosphate receptor by regulating a Rac1-cofilin signalling module
    Vanessa A. van Rahden, Kristina Brand, Juliane Najm, Jörg Heeren, Suzanne R. Pfeffer, Thomas Braulke, Kerstin Kutsche

    Human Molecular Genetics 2012, 21:5019-38 (PMID: 22907655)

    ABSTRACT: Mutations in the OCRL gene encoding the phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) 5-phosphatase OCRL cause Lowe syndrome, which is characterized by intellectual disability, cataracts, and selective proximal tubulopathy. OCRL localizes membrane bound compartments and is implicated in intracellular transport. Comprehensive analysis of clathrin-mediated endocytosis in fibroblasts of patients with LS did not reveal any difference in trafficking of epidermal growth factor, low density lipoprotein or transferrin, compared to normal fibroblasts. However, LS fibroblasts displayed reduced mannose 6-phosphate receptor (MPR)-mediated re-uptake of the lysosomal enzyme arylsulfatase B. In addition, endosome-to-trans Golgi network (TGN) transport of MPRs was decreased significantly, leading to higher levels of cell surface MPRs and their enrichment in enlarged, retromer-positive endosomes in OCRL-depleted HeLa cells. In line with the higher steady-state concentration of MPRs in the endosomal compartment in equilibrium with the cell surface, anterograde transport of the lysosomal enzyme, cathepsin D was impaired. Wild-type OCRL counteracted accumulation of MPR in endosomes in an activity-dependent manner, suggesting that PI(4,5)P(2) modulates the activity state of proteins regulated by this phosphoinositide. Indeed, we detected an increased amount of the inactive, phosphorylated form of cofilin and lower levels of the active form of PAK3 upon OCRL depletion. Levels of active Rac1 and RhoA were reduced or enhanced, respectively. Overexpression of Rac1 rescued both enhanced levels of phosphorylated cofilin and MPR accumulation in enlarged endosomes. Our data suggest that PI(4,5)P(2) dephosphorylation through OCRL regulates a Rac1-cofilin signaling cascade implicated in MPR trafficking from endosomes to the TGN.

    STATEMENT: "Our work describes a new regulatory mechanism of how deficiency of OCRL (oculocerebrorenal syndrome of Lowe) leads to abnormal trafficking processes in the cell. We identified a yet unappreciated connection between molecules implicated in intracellular transport processes and those required for reorganization of the actin cytoskeleton and demonstrate that the catalytic activity of OCRL regulates this pathway. Collectively, our data shed new light on the molecular basis underlying the rare X-linked oculocerebrorenal syndrome of Lowe. This was an interdisciplinary work between the Institute of Human Genetics, the Department of Biochemistry and Molecular Cell Biology and the Department of Biochemistry, Children's Hospital, at the University Medical Center Hamburg-Eppendorf and the Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA."

    BACKGROUND: This work was part of the PhD thesis of Vanessa A. van Rahden within the DFG research training group "Sorting and Interactions Between Proteins of Subcellular Compartments" (GRK 1459), headed by Professor Dr. Thomas Braulke. The work was performed at the Institute of Human Genetics in the group of Kerstin Kutsche who holds a professorship at UKE since 2004. The team of Kerstin Kutsche has strong research interests in uncovering the genetic basis of rare human diseases and understanding their underlying pathophysiological mechanisms.

  • UKE Paper of the Month July 2011

    A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolism
    Marschner K, Kollmann K, Schweizer M, Braulke T, Pohl S

    Science 2011, 333:87-90 (PMID:21719679)

    ABSTRACT: Mucolipidosis II is a severe lysosomal storage disorder caused by defects in the alpha and beta subunits of the hexameric N-acetylglucosamine-1-phosphotransferase complex essential for the formation of the mannose 6-phosphate targeting signal on lysosomal enzymes. Cleavage of the membrane-bound alpha/beta-subunit precursor by an unknown protease is required for catalytic activity. Here we found that the alpha/beta-subunit precursor is cleaved by the site-1 protease (S1P) that activates sterol regulatory element-binding proteins in response to cholesterol deprivation. S1P-deficient cells failed to activate the alpha/beta-subunit precursor and exhibited a mucolipidosis II-like phenotype. Thus, S1P functions in the biogenesis of lysosomes, and lipid-independent phenotypes of S1P deficiency may be caused by lysosomal dysfunction.

    STATEMENT: “Mucolipidosis II (MLII) is a severe inherited lysosomal storage disorder affecting several organs. The disease is caused by mutations in the phosphotransferase complex involved in the formation of a mannose 6-phosphate targeting signal on lysosomal proteins. Biochemically ML II is characterized by missorting of multiple lysosomal enzymes, dysfunctional lysosomes and accumulation of nondegraded material in lysosomes. In the present study we have identified a protease, site-1-protease (S1P), that cleaves the phosphotransferase precursor protein required for activation of the phosphotransferase. Cells deficient of S1P exhibit identical biochemical properties as phosphotransferase defective cells. S1P plays a crucial role in regulating lipid metabolism, cholesterol homeostasis, and viral pathogenesis. Thus, our findings are important for current therapy approaches for cardiovascular diseases and viral infections based on S1P inhibition.”

    BACKGROUND: This work was performed at the Department of Biochemistry, Children´s Hospital in the group of Thomas Braulke in collaboration with Michaela Schweizer of the Center for Molecular Neurobiology. The study was part of the PhD thesis of Katrin Marschner supervised by Sandra Pohl and was supported by the DFG (GRK1459 and SFB877). Thomas Braulke's group is interested in the biogenesis and function of lysosomes, and inherited lysosomal storage diseases.