| First Author | Zhang YQ | Year | 2012 |
| Journal | Neuron | Volume | 74 |
| Issue | 1 | Pages | 136-50 |
| PubMed ID | 22500636 | Mgi Jnum | J:188392 |
| Mgi Id | MGI:5440403 | Doi | 10.1016/j.neuron.2012.01.029 |
| Citation | Zhang YQ, et al. (2012) Identification of CSPalpha clients reveals a role in dynamin 1 regulation. Neuron 74(1):136-50 |
| abstractText | Cysteine string protein alpha (CSPalpha), a presynaptic cochaperone for Hsc70, is required for synapse maintenance. Deletion of CSPalpha leads to neuronal dysfunction, synapse loss, and neurodegeneration. We utilized unbiased, systematic proteomics to identify putative CSPalpha protein clients. We found 22 such proteins whose levels are selectively decreased in CSPalpha knockout synapses. Of these putative CSPalpha protein clients, two directly bind to the CSPalpha 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 CSPalpha regulates the stability of client proteins and synaptic vesicle number. Our analysis of CSPalpha-dynamin 1 interactions reveals unexpectedly that CSPalpha regulates the polymerization of dynamin 1. CSPalpha, 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. |
