title: Motorneurons require cysteine string protein-α to maintain the readily releasable vesicular pool and synaptic vesicle recycling.
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.
authors.affiliation: Universidad de Sevilla and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas-CIBERNED, 41013 Sevilla, Spain. jrozas@us.es
authors.forename: José Luis
authors.initials: JL
authors.lastname: Rozas
authors.forename: Leonardo
authors.initials: L
authors.lastname: Gómez-Sánchez
authors.forename: Josif
authors.initials: J
authors.lastname: Mircheski
authors.forename: Pedro
authors.initials: P
authors.lastname: Linares-Clemente
authors.forename: José Luis
authors.initials: JL
authors.lastname: Nieto-González
authors.forename: M Eugenio
authors.initials: ME
authors.lastname: Vázquez
authors.forename: Rafael
authors.initials: R
authors.lastname: Luján
authors.forename: Rafael
authors.initials: R
authors.lastname: Fernández-Chacón
mesh_terms: D000818:Animals; D005089:Exocytosis / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism* / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000378:metabolism / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism
chemical_list: D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D050825:Synaptosomal-Associated Protein 25; C088460:cysteine string protein; C514578:synaptopHIuorin; D049452:Green Fluorescent Proteins