Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans

Gracheva, E. O., Burdina, A. O., Holgado, A. M., Berthelot-Grosjean, M., Ackley, B. D., Hadwiger, G., Nonet, M. L., Weimer, R. M., Richmond, J. E. (2006) Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans. PLoS Biology, 4 (8). pp. 1426-1437. ISSN 15457885

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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. © 2006 Gracheva et al.

Item Type: Paper
Subjects: organism description > animal > C elegans
Investigative techniques and equipment > electrophysiology
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > exotysosis
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
CSHL Authors:
Communities: CSHL labs > Svoboda lab
Depositing User: CSHL Librarian
Date: 2006
Date Deposited: 14 Dec 2011 17:33
Last Modified: 13 Apr 2018 19:25
PMCID: PMC1514790
Related URLs:
URI: https://repository.cshl.edu/id/eprint/22802

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