The betagamma subunits of heterotrimeric G proteins acquire detergent insolubility directly at the plasma membrane.

The subunits of heterotrimeric G proteins, G alpha and G betagamma, are found in association with detergent-resistant domains in most mammalian cell types, implicating such domains in G protein-coupled signaling. The pathway by which the betagamma complexes are targeted to these detergent-resistant domains was unaffected by the brefeldin A-imposed block on endoplasmic reticulum-to-Golgi transport. We have used subcellular fractionation and beta subunit-specific immunoprecipitation to localize the acquisition of detergent insolubility of newly synthesized betagamma complexes. The beta subunits cofractionate with plasma membranes, and acquire detergent insolubility coincident with arrival in the plasma membrane fractions. This association was not affected by phorbol 12-myristate 13-acetate-induced activation of Protein kinase C.