Article
The synaptic vesicle protein CSP alpha prevents presynaptic degeneration
Author/s | Fernández-Chacón, Rafael
Wolfel, M. Nishimune, H. Tabares, Lucía Schmitz, Frank Castellano-Munoz, M. Rosenmund, Christian Montesinos Gutiérrez, María Luz Sudhof, TC |
Department | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica |
Publication Date | 2004-04-22 |
Deposit Date | 2023-05-22 |
Published in |
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Abstract | Cysteine string protein α (CSPα)—an abundant synaptic vesicle protein that contains a DNA-J domain characteristic of Hsp40 chaperones—is thought to regulate Ca2+ channels and/or synaptic vesicle exocytosis. We now show ... Cysteine string protein α (CSPα)—an abundant synaptic vesicle protein that contains a DNA-J domain characteristic of Hsp40 chaperones—is thought to regulate Ca2+ channels and/or synaptic vesicle exocytosis. We now show that, in young mice, deletion of CSPα does not impair survival and causes no significant changes in presynaptic Ca2+ currents or synaptic vesicle exocytosis as measured in the Calyx of Held synapse. At 2–4 weeks of age, however, CSPα-deficient mice develop a progressive, fatal sensorimotor disorder. The neuromuscular junctions and Calyx synapses of CSPα-deficient mice exhibit increasing neurodegenerative changes, synaptic transmission becomes severely impaired, and the mutant mice die at ∼2 months of age. Our data suggest that CSPα is not essential for the normal operation of Ca2+ channels or exocytosis but acts as a presynaptic chaperone that maintains continued synaptic function, raising the possibility that enhanced CSPα function could attenuate neurodegenerative diseases. |
Citation | Fernández-Chacón, R., Wolfel, M., Nishimune, H., Tabares, L., Schmitz, F., Castellano-Munoz, M.,...,Sudhof, T. (2004). The synaptic vesicle protein CSP alpha prevents presynaptic degeneration. NEURON, 42 (2), 237-251. https://doi.org/10.1016/S0896-6273(04)00190-4. |
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