QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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

This Article Full Text Full Text (PDF) All Versions of this Article: E03-07-0488v1 15/5/2073    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wadehra, M. Articles by Braun, J. Search for Related Content PubMed PubMed Citation Articles by Wadehra, M. Articles by Braun, J.

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:

				K. Shimazaki, E. J. Lepin, B. Wei, A. K. Nagy, C. P. Coulam, S. Mareninov, M. Fu, A. M. Wu, J. D. Marks, J. Braun, et al. Diabodies Targeting Epithelial Membrane Protein 2 Reduce Tumorigenicity of Human Endometrial Cancer Cell Lines Clin. Cancer Res., November 15, 2008; 14(22): 7367 - 7377. [Abstract] [Full Text] [PDF]

				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]