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Project 6

Degradative routes of intracellular proteins in lysosomal disorders

Defects in the type III membrane proteins CLN6 and GlcNAc-1-phosphotransferase localized in the endoplasmatic reticulum (ER) and the Golgi apparatus, respectively, lead to fatal inherited forms of neurodegenerative lysosomal storage disorders. Whereas the function of CLN6 is unknown, the phosphotransferase catalyzes the key step in the mannose 6-phosphate (M6P) targeting of lysosomal enzymes. Both nclf, Cln6-deficient mice, and our novel phosphotransferase knock-in mice represent models resembling the clinical and biochemical course of the human diseases. In this project we want to investigate the role of lysosomes in the turnover and processing/ activation of both endogenous and overexpressed proteins localized in post-ER compartments and in mitochondria of neuronal cells prepared from wild-type, nclf and phosphotransferase knock-in mice. Pure lysosomal fractions will be analyzed to identify accumulating brain proteins in the storage material. Finally, the M6P proteome of nclf brain tissues will be analyzed to identify distinct disease-linked changes in M6P-containing proteins. The results are expected to provide insight into the role of lysosomes in intracellular protein degradation and tissue-specific lysosomal functions depending on the composition of M6P-containing lysosomal constituents. P>

Adress:

Dr. rer. nat. Katrin Kollmann
Dept. of Biochemistry, Children's Hospital
University Medical Center Hamburg-Eppendorf
Martinistr. 52
D-20246 Hamburg
Tel.:   + 49 40 74105 1967
FAX: + 49 40 74105 8504
E-Mail: k.kollmann@uke.uni-hamburg.de

 

Adress:

Prof. Dr. rer. nat. Thomas Braulke
Dept. of Biochemistry, Children's Hospital
University Medical Center Hamburg-Eppendorf
Martinistr. 52
D-20246 Hamburg
Tel.:   + 49 40 74105 4493
FAX: + 49 40 74105 8504
E-Mail: braulke@uke.uni-hamburg.de

 

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last update: Dieter Münch-Harrach, 11.11.2010