title: Gi/o signaling and the palmitoyltransferase DHHC2 regulate palmitate cycling and shuttling of RGS7 family-binding protein.
abstract: R7BP (RGS7 family-binding protein) has been proposed to function in neurons as a palmitoylation-regulated protein that shuttles heterodimeric, G(i/o)α-specific GTPase-activating protein (GAP) complexes composed of Gβ5 and RGS7 (R7) isoforms between the plasma membrane and nucleus. To test this hypothesis we studied R7BP palmitoylation and localization in neuronal cells. We report that R7BP undergoes dynamic, signal-regulated palmitate turnover; the palmitoyltransferase DHHC2 mediates de novo and turnover palmitoylation of R7BP; DHHC2 silencing redistributes R7BP from the plasma membrane to the nucleus; and G(i/o) signaling inhibits R7BP depalmitoylation whereas G(i/o) inactivation induces nuclear accumulation of R7BP. In concert with previous evidence, our findings suggest that agonist-induced changes in palmitoylation state facilitate GAP action by (i) promoting Giα depalmitoylation to create optimal GAP substrates, and (ii) inhibiting R7BP depalmitoylation to stabilize membrane association of R7-Gβ5 GAP complexes. Regulated palmitate turnover may also enable R7BP-bound GAPs to shuttle between sites of low and high G(i/o) activity or the plasma membrane and nucleus, potentially providing spatio-temporal control of signaling by G(i/o)-coupled receptors.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Lixia
authors.initials: L
authors.lastname: Jia
authors.forename: Maurine E
authors.initials: ME
authors.lastname: Linder
authors.forename: Kendall J
authors.initials: KJ
authors.lastname: Blumer
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D054878:Lipoylation / Q000502:physiology*; D019308:Palmitic Acid / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D020710:RGS Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D044387:GTP-Binding Protein beta Subunits; D047908:Intracellular Signaling Peptides and Proteins; D020710:RGS Proteins; C542323:RGS7BP protein, human; D025521:Tumor Suppressor Proteins; D019308:Palmitic Acid; D000217:Acyltransferases; C532036:ZDHHC2 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go