title: The synaptic vesicle protein CSP alpha prevents presynaptic degeneration.
abstract: Cysteine string protein alpha (CSPalpha)--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 CSPalpha 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, CSPalpha-deficient mice develop a progressive, fatal sensorimotor disorder. The neuromuscular junctions and Calyx synapses of CSPalpha-deficient mice exhibit increasing neurodegenerative changes, synaptic transmission becomes severely impaired, and the mutant mice die at approximately 2 months of age. Our data suggest that CSPalpha 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 CSPalpha function could attenuate neurodegenerative diseases.
authors.affiliation: Center for Basic Neuroscience, Department of Molecular Genetics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75390, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Fernández-Chacón
authors.forename: Markus
authors.initials: M
authors.lastname: Wölfel
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishimune
authors.forename: Lucia
authors.initials: L
authors.lastname: Tabares
authors.forename: Frank
authors.initials: F
authors.lastname: Schmitz
authors.forename: Manuel
authors.initials: M
authors.lastname: Castellano-Muñoz
authors.forename: Christian
authors.initials: C
authors.lastname: Rosenmund
authors.forename: Maria L
authors.initials: ML
authors.lastname: Montesinos
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sanes
authors.forename: Ralf
authors.initials: R
authors.lastname: Schneggenburger
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Südhof
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins; C088460:cysteine string protein