文摘
| Figures/TablesFigures/Tables | ReferencesReferences
Summary
Cysteine string protein ¦Á (CSP¦Á), a presynaptic cochaperone for Hsc70, is required for synapse maintenance. Deletion of CSP¦Á leads to neuronal dysfunction, synapse loss, and neurodegeneration. We utilized unbiased, systematic proteomics to identify putative CSP¦Á protein clients. We found 22 such proteins whose levels are selectively decreased in CSP¦Á knockout synapses. Of these putative CSP¦Á protein clients, two directly bind to the CSP¦Á chaperone complex and are bona fide clients. They are the t-SNARE SNAP-25 and the GTPase dynamin 1, which are necessary for synaptic vesicle fusion and fission, respectively. Using hippocampal cultures, we show that CSP¦Á regulates the stability of client proteins and synaptic vesicle number. Our analysis of CSP¦Á-dynamin 1 interactions reveals unexpectedly that CSP¦Á regulates the polymerization of dynamin 1. CSP¦Á, therefore, participates in synaptic vesicle endocytosis and may facilitate exo- and endocytic coupling. These findings advance the understanding of how synapses are functionally and structurally maintained.
