Document Detail


CGI-58, the causative gene for Chanarin-Dorfman syndrome, mediates acylation of lysophosphatidic acid.
MedLine Citation:
PMID:  18606822     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
cgi-58 (comparative gene identification-58) is a member of alpha/beta-hydrolase family of proteins. Mutations in CGI-58 are shown to be responsible for a rare genetic disorder known as Chanarin-Dorfman syndrome, characterized by an excessive accumulation of triacylglycerol in several tissues and ichthyosis. We have earlier reported that YLR099c encoding Ict1p in Saccharomyces cerevisiae can acylate lysophosphatidic acid to phosphatidic acid. Here we report that human CGI-58 is closely related to ICT1. To understand the biochemical function of cgi-58, the gene was overexpressed in Escherichia coli, and the purified recombinant protein was found to specifically acylate lysophosphatidic acid in an acyl-CoA-dependent manner. Overexpression of CGI-58 in S. cerevisiae showed an increase in the formation of phosphatidic acid resulting in an overall increase in the total phospholipids. However, the triacylglycerol level was found to be significantly reduced. In addition, the physiological significance of cgi-58 in mice white adipose tissue was studied. We found soluble lysophosphatidic acid acyltransferase activity in mouse white adipose tissue. Immunoblot analysis using anti-Ict1p antibodies followed by mass spectrometry of the immunocross-reactive protein in lipid droplets revealed its identity as cgi-58. These observations suggest the existence of an alternate cytosolic phosphatidic acid biosynthetic pathway in the white adipose tissue. Collectively, these results reveal the role of cgi-58 as an acyltransferase.
Authors:
Ananda K Ghosh; Geetha Ramakrishnan; Chitraju Chandramohan; Ram Rajasekharan
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-07
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-01     Completed Date:  2008-10-20     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  24525-33     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Indian Institute of Science, Bangalore 562, India.
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MeSH Terms
Descriptor/Qualifier:
1-Acylglycerol-3-Phosphate O-Acyltransferase
Acylation
Adipose Tissue, White / enzymology
Animals
Esterases / genetics,  metabolism*
Gene Expression
Humans
Ichthyosis / enzymology*,  metabolism
Lipase / genetics,  metabolism*
Lipid Metabolism, Inborn Errors / enzymology*,  genetics
Lysophospholipids / genetics,  metabolism*
Mice
Mutation
Recombinant Proteins / genetics,  metabolism
Saccharomyces cerevisiae / enzymology,  genetics
Saccharomyces cerevisiae Proteins / genetics,  metabolism
Syndrome
Triglycerides / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Lysophospholipids; 0/Recombinant Proteins; 0/Saccharomyces cerevisiae Proteins; 0/Triglycerides; 22002-87-5/lysophosphatidic acid; EC 2.3.1.51/1-Acylglycerol-3-Phosphate O-Acyltransferase; EC 2.3.1.51/ABHD5 protein, human; EC 2.3.1.51/Abhd5 protein, mouse; EC 3.1.-/Esterases; EC 3.1.1.3/Lipase
Comments/Corrections

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