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Tomosyn Inhibits Synaptic Vesicle Priming in Caenorhabditis elegans
Gracheva, Elena O. Burdina, Anna O. Holgado, Andrea M. Berthelot-Grosjean, Martine Ackley, Brian D. Hadwiger, Gayla Nonet, Michael L. Weimer, Robby M. Richmond, Janet E.
Gracheva, Elena O.
Burdina, Anna O.
Holgado, Andrea M.
Berthelot-Grosjean, Martine
Ackley, Brian D.
Hadwiger, Gayla
Nonet, Michael L.
Weimer, Robby M.
Richmond, Janet E.
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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.
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This is the publisher's version, also available electronically from http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0040261.
Date
2006-07-25
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Public Library of Science
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Gracheva, Elena O. et al. (2006). "Tomosyn Inhibits Synaptic Vesicle Priming in Caenorhabditis elegans." PLOS Biology, 4(8):e261. http://www.dx.doi.org/10.1371/journal.pbio.0040261