Document Detail


Roles of acidic phospholipids and nucleotides in regulating membrane binding and activity of a calcium-independent phospholipase A2 isoform.
MedLine Citation:
PMID:  23007400     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Phospholipase A(2) activity plays key roles in generating lipid second messengers and regulates membrane topology through the generation of asymmetric lysophospholipids. In particular, the Group VIA phospholipase A(2) (GVIA-iPLA(2)) subfamily of enzymes functions independently of calcium within the cytoplasm of cells and has been implicated in numerous cellular processes, including proliferation, apoptosis, and membrane transport steps. However, mechanisms underlying the spatial and temporal regulation of these enzymes have remained mostly unexplored. Here, we examine the subset of Caenorhabditis elegans lipases that harbor a consensus motif common to members of the GVIA-iPLA(2) subfamily. Based on sequence homology, we identify IPLA-1 as the closest C. elegans homolog of human GVIA-iPLA(2) enzymes and use a combination of liposome interaction studies to demonstrate a role for acidic phospholipids in regulating GVIA-iPLA(2) function. Our studies indicate that IPLA-1 binds directly to multiple acidic phospholipids, including phosphatidylserine, phosphatidylglycerol, cardiolipin, phosphatidic acid, and phosphorylated derivatives of phosphatidylinositol. Moreover, the presence of these acidic lipids dramatically elevates the specific activity of IPLA-1 in vitro. We also found that the addition of ATP and ADP promote oligomerization of IPLA-1, which probably underlies the stimulatory effect of nucleotides on its activity. We propose that membrane composition and the presence of nucleotides play key roles in recruiting and modulating GVIA-iPLA(2) activity in cells.
Authors:
Kylee Morrison; Kristen Witte; Jonathan R Mayers; Amber L Schuh; Anjon Audhya
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-09-24
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-12     Completed Date:  2013-01-31     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  38824-34     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Caenorhabditis elegans
Calorimetry / methods
Cell Membrane / metabolism
Dimerization
Escherichia coli / metabolism
Gene Expression Regulation
Genome
Group VI Phospholipases A2 / metabolism
Humans
Lipid Metabolism
Liposomes / chemistry,  metabolism
Mutation
Nucleotides / chemistry*
Phospholipases / metabolism
Phospholipases A2, Calcium-Independent / chemistry,  metabolism*
Phospholipids / chemistry*,  metabolism
Protein Binding
Grant Support
ID/Acronym/Agency:
1R01GM088151/GM/NIGMS NIH HHS; R01 GM088151/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Liposomes; 0/Nucleotides; 0/Phospholipids; EC 3.1.-/Phospholipases; EC 3.1.1.4/Group VI Phospholipases A2; EC 3.1.1.4/Phospholipases A2, Calcium-Independent
Comments/Corrections

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