Munc18-1 as a key regulator of neurosecretion

Han, GA, Malintan, NT, Collins, BM, Meunier, FA and Sugita, S (2010) Munc18-1 as a key regulator of neurosecretion. Journal of Neurochemistry, 115 1: 1-10. doi:10.1111/j.1471-4159.2010.06900.x

Author Han, GA
Malintan, NT
Collins, BM
Meunier, FA
Sugita, S
Title Munc18-1 as a key regulator of neurosecretion
Journal name Journal of Neurochemistry   Check publisher's open access policy
ISSN 0022-3042
Publication date 2010-10
Sub-type Article (original research)
DOI 10.1111/j.1471-4159.2010.06900.x
Volume 115
Issue 1
Start page 1
End page 10
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell Publishing
Collection year 2011
Language eng
Formatted abstract
Munc18-1 plays essential roles in neurosecretion by interacting with syntaxin-1 and controlling the formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complex. At least three important functions of Munc18-1 have been proposed: (i) molecular chaperone of syntaxin-1 for appropriate localization and expression of syntaxin-1, (ii) priming/stimulation of the SNARE-mediated membrane fusion, and (iii) docking of large dense-core vesicles to the plasma membrane. Similarly, at least two different binding modes have been proposed for the interaction between Munc18-1 and syntaxin-1: (i) binary binding to a ‘closed’ conformation of syntaxin-1, and (ii) binding to the N-terminal peptide of syntaxin-1, which is thought to enable an interaction with the quaternary SNARE complex and/or further stabilize the binary interaction between Munc18-1 and closed syntaxin-1. Recent structural analyses have identified critical Munc18-1 residues implicated in these different modes of binding. These have recently been tested functionally in rescue experiments using Munc18-1 null neurons, chromaffin cells and Munc18-1/-2 knockdown PC12 cells, allowing remarkable progress to be made in the structural/functional understanding of Munc18-1. In this review, we summarize these recent advances and attempt to propose an updated model of the pleiotropic functions of Munc18-1 in neuroexocytosis.
© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry
Keyword Dense-core vesicles
Soluble N-ethylmaleimide-sensitive factor attachment protein receptors
Synaptic vesicles
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published under Review Article

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Created: Sun, 24 Oct 2010, 00:10:21 EST