Localization of a peripheral membrane protein: Gbetagamma targets Galpha(Z).
To explore the relative roles of protein-binding partners vs. lipid modifications in controlling membrane targeting of a typical peripheral membrane protein, Galpha(z), we directed its binding partner, betagamma, to mislocalize on mitochondria. Mislocalized betagamma directed wild-type Galpha(z) and a palmitate-lacking Galpha(z) mutant to mitochondria but did not alter localization of a Galpha(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.
Fishburn
C S
CS
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.
Pollitt
S K
SK
Bourne
H R
HR
D019943:Amino Acid Substitution; D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D019814:Myristic Acid / Q000378:metabolism; D010168:Palmitates / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
C118981:G-protein Beta gamma; D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D008563:Membrane Lipids; D008565:Membrane Proteins; D010168:Palmitates; D011993:Recombinant Fusion Proteins; D019814:Myristic Acid; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins