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Vol. 15, Issue 5, 2073-2083, May 2004

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The Tetraspan Protein EMP2 Modulates the Surface Expression of Caveolins and Glycosylphosphatidyl Inositol-linked Proteins

Madhuri Wadehra ^*, Lee Goodglick , and Jonathan Braun ^*  

^* Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California 90095; Department of Pathology and Laboratory Medicine and Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, California 90095

Submitted July 11, 2003; Revised November 14, 2003; Accepted December 9, 2003
Monitoring Editor: Reid Gilmore

Caveolae are a subset of lipid rafts enriched in glycosphingolipids and cholesterol-rich domains, but selectively lacking glycosylphosphatidyl inositol-anchored proteins (GPI-APs). Caveolin proteins are the organizing component of caveolae, but the corresponding proteins for other classes of lipid rafts are poorly defined. Epithelial membrane protein-2 (EMP2), a member of the four-transmembrane superfamily, facilitates plasma membrane delivery of certain integrins. In this study, we found by laser confocal microscopy that EMP2 was associated with GPI-APs (detected by the GPI-AP binding bacterial toxin proaerolysin). Biochemical membrane fractionation and methyl--cyclodextrin treatment demonstrated that this association occurred within lipid rafts. EMP2 did not associate with caveolin-bearing membrane structures, and recombinant overexpression of EMP2 in NIH3T3 cells decreased caveolin-1 and caveolin-2 protein levels while increasing the surface expression of GPI-APs. Conversely, a ribozyme construct that specifically cleaves the EMP2 transcript reduced surface GPI-APs and increased caveolin protein expression. These findings suggest that EMP2 facilitates the formation and surface trafficking of lipid rafts bearing GPI-APs, and reduces caveolin expression, resulting in impaired formation of caveolae.

Abbreviations used: EMP2, epithelial membrane protein-2; GPI, glycosylphosphatidylinositol;GPI-AP,glycosylphosphatidylinositol-anchored protein; GAS3, growth arrest specific-3; PMP22, peripheral myelin protein-22; MCD, methyl--cyclodextrin.

Corresponding author. E-mail address: jbraun{at}mednet.ucla.edu.

This article has been cited by other articles:

				A. Forbes, M. Wadehra, S. Mareninov, S. Morales, K. Shimazaki, L. K. Gordon, and J. Braun The Tetraspan Protein EMP2 Regulates Expression of Caveolin-1 J. Biol. Chem., September 7, 2007; 282(36): 26542 - 26551. [Abstract] [Full Text] [PDF]