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SORLA regulates calpain‐dependent degradation of synapsin
Author(s) -
Hartl Daniela,
Nebrich Grit,
Klein Oliver,
Stephanowitz Heike,
Krause Eberhard,
Rohe Michael
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.02.008
Subject(s) - synapsin , synapsin i , microbiology and biotechnology , exocytosis , biology , receptor , endocytosis , calpain , synaptic vesicle , neuroscience , biochemistry , vesicle , secretion , membrane , enzyme
Sorting‐related receptor with A‐type repeats (SORLA) is an intracellular sorting receptor in neurons and a major risk factor for Alzheimer disease. Methods Here, we performed global proteome analyses in the brain of SORLA‐deficient mice followed by biochemical and histopathologic studies to identify novel neuronal pathways affected by receptor dysfunction. Results We demonstrate that the lack of SORLA results in accumulation of phosphorylated synapsins in cortex and hippocampus. We propose an underlying molecular mechanism by demonstrating that SORLA interacts with phosphorylated synapsins through 14‐3‐3 adaptor proteins to deliver synapsins to calpain‐mediated proteolytic degradation. Discussion Our results suggest a novel function for SORLA which is in control of synapsin degradation, potentially impacting on synaptic vesicle endocytosis and/or exocytosis.