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PMID: 25280637 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

PI(4,5)P₂-binding effector proteins for vesicle exocytosis.

Biochimica et biophysica acta ·Vol. 1851 ·No. 6 ·2015-06-00 ·Pages 785-93

Martin TF

Abstract

PI(4,5)P₂participates directly in priming and possibly in fusion steps of Ca²⁺-triggered vesicle exocytosis. High concentration nanodomains of PI(4,5)P₂reside on the plasma membrane of neuroendocrine cells. A subset of vesicles that co-localize with PI(4,5)P₂ domains appear to undergo preferential exocytosis in stimulated cells. PI(4,5)P₂directly regulates vesicle exocytosis by recruiting and activating PI(4,5)P₂-binding proteins that regulate SNARE protein function including CAPS, Munc13-1/2, synaptotagmin-1, and other C2 domain-containing proteins. These PI(4,5)P₂effector proteins are coincidence detectors that engage in multiple interactions at vesicle exocytic sites. The SNARE protein syntaxin-1 also binds to PI(4,5)P₂, which promotes clustering, but an activating role for PI(4,5)P₂in syntaxin-1 function remains to be fully characterized. Similar principles underlie polarized constitutive vesicle fusion mediated in part by the PI(4,5)P₂-binding subunits of the exocyst complex (Sec3, Exo70). Overall, focal vesicle exocytosis occurs at sites landmarked by PI(4,5)P2, which serves to recruit and/or activate multifunctional PI(4,5)P₂-binding proteins. This article is part of a Special Issue entitled Phosphoinositides.

Keywords
CAPS/CADPS Munc13 Phosphatidylinositol(4 5)bisphosphate SNARE protein Synaptotagmin Vesicle exocytosis
MeSH Terms
Animals Biological Transport Calcium/metabolism Calcium-Binding Proteins/genetics,metabolism Exocytosis/genetics Gene Expression Regulation Nerve Tissue Proteins/genetics,metabolism Phosphatidylinositol 4,5-Diphosphate/metabolism Protein Binding Signal Transduction Synaptotagmin I/genetics,metabolism Syntaxin 1/genetics,metabolism Transport Vesicles/chemistry,metabolism Vesicular Transport Proteins/genetics,metabolism
Chemicals
Calcium-Binding Proteins Nerve Tissue Proteins Phosphatidylinositol 4,5-Diphosphate Synaptotagmin I Syntaxin 1 Vesicular Transport Proteins Calcium
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Martin Thomas F J
Biochemistry Department, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706, USA. Electronic address: [email protected].
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Article Info
Journal
Biochimica et biophysica acta
Abbr.
Biochim Biophys Acta
ISSN
0006-3002
DOI
10.1016/j.bbalip.2014.09.017
Email
[email protected]
Published
2015-06-00
Epub
2014-00-02
Pages
785-93
Language
English
Region
Netherlands
NLM ID
0217513
PMCID
PMC4380529
Subset
IM
Grants
NIGMS NIH HHS · R01 GM119158 · United States
NIDDK NIH HHS · R37 DK025861 · United States
NIDDK NIH HHS · R01 DK025861 · United States
NIDDK NIH HHS · DK040428 · United States
NIDDK NIH HHS · DK025861 · United States
NIDDK NIH HHS · R01 DK040428 · United States
External Links
PubMed source DOI: 10.1016/j.bbalip.2014.09.017 PMC Full Text
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