Munc18-dependent regulation of synaptic vesicle exocytosis by syntaxin-1A in hippocampal neurons. Academic Article uri icon

Overview

abstract

  • The fusion of secretory vesicles with the plasma membrane requires the formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes between the vesicle-SNARE vesicle-associated membrane protein present on the vesicular membrane and the target-SNAREs SNAP-25 and syntaxin-1A. Syntaxin-1A fluctuates between an open and closed form allowing it to selectively bind to different biological effectors in different conformations. In the open form, it can participate in SNARE complex formation, however, in the closed form it negatively regulates N- and P/Q-type voltage-dependent calcium channels, and is capable of inhibiting calcium influx. Thus paradoxically, syntaxin appears to have both positive and negative roles in controlling calcium-driven synaptic vesicle fusion at synaptic terminals. We show here that overexpression of syntaxin-1A inhibited exocytosis, in a manner that could be rescued by either elevating or reducing external calcium, or increasing action potential firing frequency. Elevating the level of Munc18 by coexpression with syntaxin-1A also abolished this inhibition, suggesting that Munc18 serves to limit the negative regulatory role of syntaxin by binding to, and thereby buffering, its closed form. Our results also indicate that syntaxin can control the frequency-response characteristics of the presynaptic fusion machinery.

publication date

  • January 25, 2005

Research

keywords

  • Antigens, Surface
  • Exocytosis
  • Hippocampus
  • Nerve Tissue Proteins
  • Synaptic Vesicles
  • Vesicular Transport Proteins

Identity

Scopus Document Identifier

  • 13844294351

Digital Object Identifier (DOI)

  • 10.1016/j.neuropharm.2004.10.017

PubMed ID

  • 15721169

Additional Document Info

volume

  • 48

issue

  • 3