First Author | Rozas JL | Year | 2012 |
Journal | Neuron | Volume | 74 |
Issue | 1 | Pages | 151-65 |
PubMed ID | 22500637 | Mgi Jnum | J:188391 |
Mgi Id | MGI:5440402 | Doi | 10.1016/j.neuron.2012.02.019 |
Citation | Rozas JL, et al. (2012) Motorneurons require cysteine string protein-alpha to maintain the readily releasable vesicular pool and synaptic vesicle recycling. Neuron 74(1):151-65 |
abstractText | Cysteine string protein-alpha (CSP-alpha) is a synaptic vesicle protein that prevents activity-dependent neurodegeneration by poorly understood mechanisms. We have studied the synaptic vesicle cycle at the motor nerve terminals of CSP-alpha knock-out mice expressing the synaptopHluorin transgene. Mutant nerve terminals fail to sustain prolonged release and the number of vesicles available to be released decreases. Strikingly, the SNARE protein SNAP-25 is dramatically reduced. In addition, endocytosis during the stimulus fails to maintain the size of the recycling synaptic vesicle pool during prolonged stimulation. Upon depolarization, the styryl dye FM 2-10 becomes trapped and poorly releasable. Consistently with the functional results, electron microscopy analysis revealed characteristic features of impaired synaptic vesicle recycling. The unexpected defect in vesicle recycling in CSP-alpha knock-out mice provides insights into understanding molecular mechanisms of degeneration in motor nerve terminals. |