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PMID: 11251080 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Segregation of heterotrimeric G proteins in cell surface microdomains. G(q) binds caveolin to concentrate in caveolae, whereas G(i) and G(s) target lipid rafts by default.

Molecular biology of the cell ·Vol. 12 ·No. 3 ·2001-03-00 ·Pages 685-98

Oh P, Schnitzer JE

Abstract

Select lipid-anchored proteins such as glycosylphosphatidylinositol (GPI)-anchored proteins and nonreceptor tyrosine kinases may preferentially partition into sphingomyelin-rich and cholesterol-rich plasmalemmal microdomains, thereby acquiring resistance to detergent extraction. Two such domains, caveolae and lipid rafts, are morphologically and biochemically distinct, contain many signaling molecules, and may function in compartmentalizing cell surface signaling. Subfractionation and confocal immunofluorescence microscopy reveal that, in lung tissue and in cultured endothelial and epithelial cells, heterotrimeric G proteins (G(i), G(q), G(s), and G(betagamma)) target discrete cell surface microdomains. G(q) specifically concentrates in caveolae, whereas G(i) and G(s) concentrate much more in lipid rafts marked by GPI-anchored proteins (5' nucleotidase and folate receptor). G(q), apparently without G(betagamma) subunits, stably associates with plasmalemmal and cytosolic caveolin. G(i) and G(s) interact with G(betagamma) subunits but not caveolin. G(i) and G(s), unlike G(q), readily move out of caveolae. Thus, caveolin may function as a scaffold to trap, concentrate, and stabilize G(q) preferentially within caveolae over lipid rafts. In N2a cells lacking caveolae and caveolin, G(q), G(i), and G(s) all concentrate in lipid rafts as a complex with G(betagamma). Without effective physiological interaction with caveolin, G proteins tend by default to segregate in lipid rafts. The ramifications of the segregated microdomain distribution and the G(q)-caveolin complex without G(betagamma) for trafficking, signaling, and mechanotransduction are discussed.

MeSH Terms
Animals Binding Sites Caveolae/metabolism Caveolin 1 Caveolins/metabolism Cell Membrane/metabolism Cells, Cultured GTP-Binding Protein alpha Subunits, Gi-Go/metabolism GTP-Binding Protein alpha Subunits, Gq-G11 GTP-Binding Protein alpha Subunits, Gs/metabolism Heterotrimeric GTP-Binding Proteins/metabolism In Vitro Techniques Lung/metabolism Membrane Lipids/metabolism Microscopy, Fluorescence Protein Binding Rats
Chemicals
Cav1 protein, rat Caveolin 1 Caveolins Membrane Lipids GTP-Binding Protein alpha Subunits, Gi-Go GTP-Binding Protein alpha Subunits, Gq-G11 GTP-Binding Protein alpha Subunits, Gs Heterotrimeric GTP-Binding Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Oh P
Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
Schnitzer J E
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.12.3.685
Published
2001-03-00
Pages
685-98
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC30973
Subset
IM
Grants
NHLBI NIH HHS · R01 HL052766 · United States
NHLBI NIH HHS · R01 HL058216 · United States
NHLBI NIH HHS · HL-52766 · United States
NHLBI NIH HHS · HL-58216 · United States
External Links
PubMed source DOI: 10.1091/mbc.12.3.685 PMC Full Text View journal details
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