Localization of a peripheral membrane protein: Gβγ targets Gα(Z)

To explore the relative roles of protein-binding partners vs. lipid modifications in controlling membrane targeting of a typical peripheral membrane protein, Gα(z), we directed its binding partner, βγ, to mislocalize on mitochondria. Mislocalized βγ directed wild-type Gα(z) and a palmitate-lacking Gα(z) mutant to mitochondria but did not alter localization of a Gα(z) mutant lacking both myristate and palmitate. Thus, in this paradigm, a protein–protein interaction controls targeting of a peripheral membrane protein to the proper compartment, whereas lipid modifications stabilize interactions of proteins with membranes and with other proteins.