The membrane-spanning domains of caveolins-1 and -2 mediate the formation of caveolin hetero-oligomers. Implications for the assembly of caveolae membranes in vivo.
The mammalian caveolin gene family consists of caveolins-1, -2, and -3. The expression of caveolin-3 is muscle-specific. In contrast, caveolins-1 and -2 are co-expressed, and they form a hetero-oligomeric complex in many cell types, with particularly high levels in adipocytes, endothelial cells, and fibroblasts. These caveolin hetero-oligomers are thought to represent the functional assembly units that drive caveolae formation in vivo. Here, we investigate the mechanism by which caveolins-1 and -2 form hetero-oligomers. We reconstituted this reciprocal interaction in vivo and in vitro using a variety of complementary approaches, including the generation of glutathione S-transferase fusion proteins and synthetic peptides. Taken together, our results indicate that the membrane-spanning domains of both caveolins-1 and -2 play a critical role in mediating their ability to interact with each other. This is the first demonstration that these unusual membrane-spanning regions found in the caveolin family play a specific role in protein-protein interactions.
Das
K
K
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Lewis
R Y
RY
Scherer
P E
PE
Lisanti
M P
MP
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins; D002462:Cell Membrane / Q000737:chemistry; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000302:isolation & purification; D018604:Epitope Mapping; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011487:Protein Conformation; D017433:Protein Structure, Secondary
C495541:Cav1 protein, mouse; D051242:Caveolin 1; D051243:Caveolin 2; D022461:Caveolins; D018076:DNA, Complementary; D008565:Membrane Proteins