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Munc18‐1 as a key regulator of neurosecretion
Author(s) -
Han Gayoung A.,
Malintan Nancy T.,
Collins Brett M.,
Meunier Frederic A.,
Sugita Shuzo
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06900.x
Subject(s) - snare complex , syntaxin , microbiology and biotechnology , syntaxin 3 , vesicle fusion , biology , regulator , lipid bilayer fusion , chemistry , synaptic vesicle , membrane protein , vesicle , membrane , biochemistry , gene
J. Neurochem. (2010) 115 , 1–10. 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.