Identification of a novel splicing isoform of murine CGI-58

Edited by Robert Barouki

Received 22 October 2009; received in revised form 13 December 2009; accepted 23 December 2009. published online 18 January 2010.

Abstract

The comparative gene identification-58 (CGI-58) gene, mutations of which are linked to Chanarin-Dorfman syndrome, encodes a protein of the α/β hydrolase domain subfamily. We report here a new alternative splicing isoform of the murine CGI-58 gene, termed mCGI-58S. Sequence comparison indicates the lack of second and third exons in this cDNA variant. While the full-length protein displayed perilipin-dependent localization to lipid droplets, mCGI-58S showed a predominant cytoplasmic staining when expressed in cells. mCGI-58S was incapable of activating adipose triglyceride lipase but retained the capacity to acylate lysophosphatidic acid. Overexpression of mCGI-58S failed to promote lipid droplet turnover and loss of intracellular triacylglycerols. These results suggest that this splicing event may be involved in the regulation of lipid homeostasis.

Abbreviations: CGI-58, comparative gene identification-58, CDS, Chanarin-Dorfman syndrome, LPA, lysophosphatidic acid, PA, phosphatidic acid, ATGL, adipose triglyceride lipase, TAG, triacylglycerol

Keywords: Neutral lipid storage disease, Lipolysis, Triacylglycerol, Lipid droplet, Lysophosphatidic acid

Department of Pediatrics, University of Kentucky, Lexington, KY, USA

Kentucky Pediatric Research Institute, University of Kentucky, Lexington, KY, USA

Corresponding author. Address: Department of Pediatrics, University of Kentucky, BBSRB B357, 741 South Limestone Street, Lexington, KY 40536-0509, USA. Fax: +1 859 257 2120.

PII: S0014-5793(10)00044-X

doi:10.1016/j.febslet.2009.12.058

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