Syntaxin 1B, but Not Syntaxin 1A, Is Necessary for the Regulation of Synaptic Vesicle Exocytosis and of the Readily Releasable Pool at Central Synapses

PLoS One. 2014 Feb 28;9(2):e90004. doi: 10.1371/journal.pone.0090004. eCollection 2014.

Abstract

Two syntaxin 1 (STX1) isoforms, HPC-1/STX1A and STX1B, are coexpressed in neurons and function as neuronal target membrane (t)-SNAREs. However, little is known about their functional differences in synaptic transmission. STX1A null mutant mice develop normally and do not show abnormalities in fast synaptic transmission, but monoaminergic transmissions are impaired. In the present study, we found that STX1B null mutant mice died within 2 weeks of birth. To examine functional differences between STX1A and 1B, we analyzed the presynaptic properties of glutamatergic and GABAergic synapses in STX1B null mutant and STX1A/1B double null mutant mice. We found that the frequency of spontaneous quantal release was lower and the paired-pulse ratio of evoked postsynaptic currents was significantly greater in glutamatergic and GABAergic synapses of STX1B null neurons. Deletion of STX1B also accelerated synaptic vesicle turnover in glutamatergic synapses and decreased the size of the readily releasable pool in glutamatergic and GABAergic synapses. Moreover, STX1A/1B double null neurons showed reduced and asynchronous evoked synaptic vesicle release in glutamatergic and GABAergic synapses. Our results suggest that although STX1A and 1B share a basic function as neuronal t-SNAREs, STX1B but not STX1A is necessary for the regulation of spontaneous and evoked synaptic vesicle exocytosis in fast transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Evoked Potentials / physiology
  • Exocytosis / physiology*
  • Gene Expression Regulation
  • Glutamic Acid / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Neurons / cytology
  • Neurons / metabolism*
  • Synapses / physiology*
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism
  • Syntaxin 1 / genetics
  • Syntaxin 1 / metabolism*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Stx1a protein, mouse
  • Syntaxin 1
  • Glutamic Acid
  • gamma-Aminobutyric Acid

Grant support

This study was financially supported by a JSPS Grant-in-Aid for Scientific Research (C) to TM (No. 24500462) and TF (No. 22500338), a JSPS Grant-in-Aid for Scientific Research (B) to KA (No. 24300142), and a Grant-in-Aid from the Promotion and Mutual Aid Cooperation for Private Schools of Japan to KA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.