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PMID: 22374089 Published · ppublish English Journal Article Review

Role of PI(4,5)P(2) in vesicle exocytosis and membrane fusion.

Sub-cellular biochemistry ·Vol. 59 ·2012-00-00 ·Pages 111-30

Martin TF

Abstract

A role for phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) in membrane fusion was originally identified for regulated dense-core vesicle exocytosis in neuroendocrine cells. Subsequent studies demonstrated essential roles for PI(4,5)P(2) in regulated synaptic vesicle and constitutive vesicle exocytosis. For regulated dense-core vesicle exocytosis, PI(4,5)P(2) appears to be primarily required for priming, a stage in vesicle exocytosis that follows vesicle docking and precedes Ca(2) (+)-triggered fusion. The priming step involves the organization of SNARE protein complexes for fusion. A central issue concerns the mechanisms by which PI(4,5)P(2) exerts an essential role in membrane fusion events at the plasma membrane. The observed microdomains of PI(4,5)P(2) in the plasma membrane of neuroendocrine cells at fusion sites has suggested possible direct effects of the phosphoinositide on membrane curvature and tension. More likely, PI(4,5)P(2) functions in vesicle exocytosis as in other cellular processes to recruit and activate PI(4,5)P(2)-binding proteins. CAPS and Munc13 proteins, which bind PI(4,5)P(2) and function in vesicle priming to organize SNARE proteins, are key candidates as effectors for the role of PI(4,5)P(2) in vesicle priming. Consistent with roles prior to fusion that affect SNARE function, subunits of the exocyst tethering complex involved in constitutive vesicle exocytosis also bind PI(4,5)P(2). Additional roles for PI(4,5)P(2) in fusion pore dilation have been described, which may involve other PI(4,5)P(2)-binding proteins such as synaptotagmin. Lastly, the SNARE proteins that mediate exocytic vesicle fusion contain highly basic membrane-proximal domains that interact with acidic phospholipids that likely affect their function.

MeSH Terms
Animals Calcium/metabolism Calcium-Binding Proteins/metabolism Cell Membrane/metabolism Eukaryotic Cells/metabolism Exocytosis Humans Membrane Fusion Phosphatidylinositol 4,5-Diphosphate/metabolism Qa-SNARE Proteins/metabolism Signal Transduction Synaptosomal-Associated Protein 25/metabolism Synaptotagmins/metabolism Transport Vesicles/metabolism Vesicle-Associated Membrane Protein 2/metabolism
Chemicals
CAPS protein, human Calcium-Binding Proteins Phosphatidylinositol 4,5-Diphosphate Qa-SNARE Proteins Synaptosomal-Associated Protein 25 Vesicle-Associated Membrane Protein 2 Synaptotagmins Calcium
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Martin Thomas F J
Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, 53706, Madison, WI, U.S.A, tfmartin@wisc.edu.
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Article Info
Journal
Sub-cellular biochemistry
Abbr.
Subcell Biochem
ISSN
0306-0225
DOI
10.1007/978-94-007-3015-1_4
Email
tfmartin@wisc.edu
Published
2012-00-00
Pages
111-30
Language
English
Region
United States
NLM ID
0316571
PMCID
PMC3978774
Subset
IM
Grants
NIDDK NIH HHS · R01 DK025861 · United States
NIDDK NIH HHS · R01 DK040428 · United States
External Links
PubMed source DOI: 10.1007/978-94-007-3015-1_4 PMC Full Text
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