Functionally and spatially distinct modes of munc18-syntaxin 1 interaction

Colin Rickman, Claire N Medine, Axel Bergmann, Rory R Duncan

Research output: Contribution to journalArticle

Abstract

Eukaryotic membrane trafficking is a conserved process under tight temporal and spatial regulation in which the fusion of membranes is driven by the formation of the ternary SNARE complex. Syntaxin 1a, a core component of the exocytic SNARE complex in neurons and neuroendocrine cells, is regulated directly by munc18-1, its cognate Sec1p/munc18 (SM) protein. SM proteins show remarkable structural conservation throughout evolution, indicating a common binding mechanism and function. However, SM proteins possess disparate binding mechanisms and regulatory effects with munc18-1, the major brain isoform, classed as atypical in both its binding specificity and its mode. We now show that munc18-1 interacts with syntaxin 1a through two mechanistically distinct modes of binding, both in vitro and in living cells, in contrast to current models. Furthermore, these functionally divergent interactions occur at distinct cellular locations. These findings provide a molecular explanation for the multiple, spatially distinct roles of munc18-1.
LanguageEnglish
Pages12097-12103
Number of pages7
JournalJournal of Biological Chemistry
Volume282
Issue number16
DOIs
Publication statusPublished - 20 Apr 2007

Fingerprint

Munc18 Proteins
Syntaxin 1
SNARE Proteins
Neuroendocrine Cells
Membrane Fusion
Protein Isoforms
Neurons
Membranes
Brain

Keywords

  • Amino Acid Sequence
  • Brain
  • Humans
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Munc18 Proteins
  • Neurons
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Syntaxin 1
  • Time Factors
  • Vesicular Transport Proteins

Cite this

@article{971ead00cd1e4686bce96bf87f4dd1c0,
title = "Functionally and spatially distinct modes of munc18-syntaxin 1 interaction",
abstract = "Eukaryotic membrane trafficking is a conserved process under tight temporal and spatial regulation in which the fusion of membranes is driven by the formation of the ternary SNARE complex. Syntaxin 1a, a core component of the exocytic SNARE complex in neurons and neuroendocrine cells, is regulated directly by munc18-1, its cognate Sec1p/munc18 (SM) protein. SM proteins show remarkable structural conservation throughout evolution, indicating a common binding mechanism and function. However, SM proteins possess disparate binding mechanisms and regulatory effects with munc18-1, the major brain isoform, classed as atypical in both its binding specificity and its mode. We now show that munc18-1 interacts with syntaxin 1a through two mechanistically distinct modes of binding, both in vitro and in living cells, in contrast to current models. Furthermore, these functionally divergent interactions occur at distinct cellular locations. These findings provide a molecular explanation for the multiple, spatially distinct roles of munc18-1.",
keywords = "Amino Acid Sequence, Brain, Humans, Microscopy, Confocal, Molecular Sequence Data, Munc18 Proteins, Neurons, Protein Binding, Protein Interaction Mapping, Protein Isoforms, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Syntaxin 1, Time Factors, Vesicular Transport Proteins",
author = "Colin Rickman and Medine, {Claire N} and Axel Bergmann and Duncan, {Rory R}",
year = "2007",
month = "4",
day = "20",
doi = "10.1074/jbc.M700227200",
language = "English",
volume = "282",
pages = "12097--12103",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "16",

}

Functionally and spatially distinct modes of munc18-syntaxin 1 interaction. / Rickman, Colin; Medine, Claire N; Bergmann, Axel; Duncan, Rory R.

In: Journal of Biological Chemistry, Vol. 282, No. 16, 20.04.2007, p. 12097-12103.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Functionally and spatially distinct modes of munc18-syntaxin 1 interaction

AU - Rickman, Colin

AU - Medine, Claire N

AU - Bergmann, Axel

AU - Duncan, Rory R

PY - 2007/4/20

Y1 - 2007/4/20

N2 - Eukaryotic membrane trafficking is a conserved process under tight temporal and spatial regulation in which the fusion of membranes is driven by the formation of the ternary SNARE complex. Syntaxin 1a, a core component of the exocytic SNARE complex in neurons and neuroendocrine cells, is regulated directly by munc18-1, its cognate Sec1p/munc18 (SM) protein. SM proteins show remarkable structural conservation throughout evolution, indicating a common binding mechanism and function. However, SM proteins possess disparate binding mechanisms and regulatory effects with munc18-1, the major brain isoform, classed as atypical in both its binding specificity and its mode. We now show that munc18-1 interacts with syntaxin 1a through two mechanistically distinct modes of binding, both in vitro and in living cells, in contrast to current models. Furthermore, these functionally divergent interactions occur at distinct cellular locations. These findings provide a molecular explanation for the multiple, spatially distinct roles of munc18-1.

AB - Eukaryotic membrane trafficking is a conserved process under tight temporal and spatial regulation in which the fusion of membranes is driven by the formation of the ternary SNARE complex. Syntaxin 1a, a core component of the exocytic SNARE complex in neurons and neuroendocrine cells, is regulated directly by munc18-1, its cognate Sec1p/munc18 (SM) protein. SM proteins show remarkable structural conservation throughout evolution, indicating a common binding mechanism and function. However, SM proteins possess disparate binding mechanisms and regulatory effects with munc18-1, the major brain isoform, classed as atypical in both its binding specificity and its mode. We now show that munc18-1 interacts with syntaxin 1a through two mechanistically distinct modes of binding, both in vitro and in living cells, in contrast to current models. Furthermore, these functionally divergent interactions occur at distinct cellular locations. These findings provide a molecular explanation for the multiple, spatially distinct roles of munc18-1.

KW - Amino Acid Sequence

KW - Brain

KW - Humans

KW - Microscopy, Confocal

KW - Molecular Sequence Data

KW - Munc18 Proteins

KW - Neurons

KW - Protein Binding

KW - Protein Interaction Mapping

KW - Protein Isoforms

KW - Protein Structure, Tertiary

KW - Sequence Homology, Amino Acid

KW - Syntaxin 1

KW - Time Factors

KW - Vesicular Transport Proteins

U2 - 10.1074/jbc.M700227200

DO - 10.1074/jbc.M700227200

M3 - Article

VL - 282

SP - 12097

EP - 12103

JO - Journal of Biological Chemistry

T2 - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 16

ER -