The tetraspan protein EMP2 regulates expression of caveolin-1.
Caveolin-1 is the primary component of caveolae and functions in a variety of intracellular activities, including membrane trafficking and signal transduction. EMP2 (epithelial membrane protein 2) is a tetraspan protein recently identified as a novel regulator of caveolin-1 expression. In this study, we analyzed the mechanism of EMP2-mediated caveolin-1 regulation. In NIH 3T3 cells and in the human retinal pigment epithelium cell line (ARPE-19), EMP2 regulates caveolin-1 transcription and more substantially its protein levels. EMP2-mediated down-regulation of caveolin-1 does not affect caveolin-1 translational efficiency, phosphorylation, or proteasome-mediated degradation. Analysis of caveolin-1 protein half-life indicates the EMP2-mediated loss of caveolin-1 occurs rapidly. Protease inhibition and laser confocal microscopy associates this fate with specific intracellular compartmentalization, including early lysosomal delivery. These findings elucidate a new mechanism of caveolin-1 regulation and define an additional role for EMP2 as a key regulator of cell membrane composition.
Forbes
Ashley
A
Molecular Biology Institute, David Geffen School of Medicine, UCLA, Los Angeles, California 90095, USA.
Wadehra
Madhuri
M
Mareninov
Sergei
S
Morales
Shawn
S
Shimazaki
Kaori
K
Gordon
Lynn K
LK
Braun
Jonathan
J
D000818:Animals; D051242:Caveolin 1 / Q000096:biosynthesis* / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*
C495540:CAV1 protein, human; D051242:Caveolin 1; C486403:EMP2 protein, human; C113388:Emp2 protein, mouse; D008562:Membrane Glycoproteins; D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex