Hsp90 Interactions and Acylation Target the G Protein Gα12 but Not Gα13 to Lipid Rafts*

The heterotrimeric G proteins, G12and G13, are closely related in their sequences, signaling partners, and cellular effects such as oncogenic transformation and cytoskeletal reorganization. Yet G12 and G13can act through different pathways, bind different proteins, and show opposing actions on some effectors. We investigated the compartmentalization of G12 and G13 at the membrane because other G proteins reside in lipid rafts, membrane microdomains enriched in cholesterol and sphingolipids. Lipid rafts were isolated after cold, nonionic detergent extraction of cells and gradient centrifugation. Gα12 was in the lipid raft fractions, whereas Gα13 was not associated with lipid rafts. Mutation of Cys-11 on Gα12, which prevents its palmitoylation, partially shifted Gα12 from the lipid rafts. Geldanamycin treatment, which specifically inhibits Hsp90, caused a partial loss of wild-type Gα12 and a complete loss of the Cys-11 mutant from the lipid rafts and the appearance of a higher molecular weight form of Gα12 in the soluble fractions. These results indicate that acylation and Hsp90 interactions localized Gα12 to lipid rafts. Hsp90 may act as both a scaffold and chaperone to maintain a functional Gα12 only in discrete membrane domains and thereby explain some of the nonoverlapping functions of G12 and G13 and control of these potent cell regulators.

• Publication year

  2002

• Venue

  Journal of Biological Chemistry

• Publication date

  2002-09-06

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/jbc.C200383200PMID 12117999
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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