Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.23.5 (
cathepsin D
)
4,130
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
How, in the absence of a functional mannose 6-phosphate (Man-6-P)-signal-dependent transport pathway, some acid hydrolases remain sorted to endolysosomes in the brain is poorly understood. We demonstrate that
cathepsin D
binds to mouse SEZ6L2, a type 1 transmembrane protein predominantly expressed in the brain. Studies of the subcellular trafficking of SEZ6L2, and its silencing in a mouse neuroblastoma cell line reveal that SEZ6L2 is involved in the trafficking of
cathepsin D
to endosomes. Moreover, SEZ6L2 can partially correct the
cathepsin D
hypersecretion resulting from the knockdown of
UDP-GlcNAc
:lysosomal enzyme GlcNAc-1-phosphotransferase in HeLa cells (i.e. in cells that are unable to synthesize Man-6-P signals). Interestingly, cleavage of SEZ6L2 by
cathepsin D
generates an N-terminal soluble fragment that induces neurite outgrowth, whereas its membrane counterpart prevents this. Taken together, our findings highlight that SEZ6L2 can serve as receptor to mediate the sorting of
cathepsin D
to endosomes, and suggest that proteolytic cleavage of SEZ6L2 by
cathepsin D
modulates neuronal differentiation.
...
PMID:Cathepsin D and its newly identified transport receptor SEZ6L2 can modulate neurite outgrowth. 2669 17
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