1. Motorneurons require cysteine string protein-α to maintain the readily releasable vesicular pool and synaptic vesicle recycling.
- Author
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Rozas JL, Gómez-Sánchez L, Mircheski J, Linares-Clemente P, Nieto-González JL, Vázquez ME, Luján R, and Fernández-Chacón R
- Subjects
- Animals, Green Fluorescent Proteins metabolism, Mice, Mice, Knockout, Mice, Transgenic, Motor Neurons ultrastructure, Muscle, Skeletal metabolism, Muscle, Skeletal ultrastructure, Neuromuscular Junction metabolism, Neuromuscular Junction ultrastructure, Recombinant Fusion Proteins metabolism, Synaptic Vesicles ultrastructure, Synaptosomal-Associated Protein 25 metabolism, Exocytosis physiology, HSP40 Heat-Shock Proteins metabolism, Membrane Proteins metabolism, Motor Neurons metabolism, Synaptic Transmission physiology, Synaptic Vesicles metabolism
- Abstract
Cysteine string protein-α (CSP-α) 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-α 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-α knock-out mice provides insights into understanding molecular mechanisms of degeneration in motor nerve terminals., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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