title: Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans.
abstract: Caenorhabditis elegans TOM-1 is orthologous to vertebrate tomosyn, a cytosolic syntaxin-binding protein implicated in the modulation of both constitutive and regulated exocytosis. To investigate how TOM-1 regulates exocytosis of synaptic vesicles in vivo, we analyzed C. elegans tom-1 mutants. Our electrophysiological analysis indicates that evoked postsynaptic responses at tom-1 mutant synapses are prolonged leading to a two-fold increase in total charge transfer. The enhanced response in tom-1 mutants is not associated with any detectable changes in postsynaptic response kinetics, neuronal outgrowth, or synaptogenesis. However, at the ultrastructural level, we observe a concomitant increase in the number of plasma membrane-contacting vesicles in tom-1 mutant synapses, a phenotype reversed by neuronal expression of TOM-1. Priming defective unc-13 mutants show a dramatic reduction in plasma membrane-contacting vesicles, suggesting these vesicles largely represent the primed vesicle pool at the C. elegans neuromuscular junction. Consistent with this conclusion, hyperosmotic responses in tom-1 mutants are enhanced, indicating the primed vesicle pool is enhanced. Furthermore, the synaptic defects of unc-13 mutants are partially suppressed in tom-1 unc-13 double mutants. These data indicate that in the intact nervous system, TOM-1 negatively regulates synaptic vesicle priming.
authors.affiliation: Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Elena O
authors.initials: EO
authors.lastname: Gracheva
authors.forename: Anna O
authors.initials: AO
authors.lastname: Burdina
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Holgado
authors.forename: Martine
authors.initials: M
authors.lastname: Berthelot-Grosjean
authors.forename: Brian D
authors.initials: BD
authors.lastname: Ackley
authors.forename: Gayla
authors.initials: G
authors.lastname: Hadwiger
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nonet
authors.forename: Robby M
authors.initials: RM
authors.lastname: Weimer
authors.forename: Janet E
authors.initials: JE
authors.lastname: Richmond
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D004594:Electrophysiology; D008969:Molecular Sequence Data; D009154:Mutation; D009469:Neuromuscular Junction / Q000502:physiology; D010641:Phenotype; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics / Q000502:physiology; D016415:Sequence Alignment; D013572:Synaptic Vesicles / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D029742:Caenorhabditis elegans Proteins; D020033:Protein Isoforms; C513301:tom-1 protein, C elegans