Palmitoylation regulates plasma membrane-nuclear shuttling of R7BP, a novel membrane anchor for the RGS7 family.
The RGS7 (R7) family of RGS proteins bound to the divergent Gbeta subunit Gbeta5 is a crucial regulator of G protein-coupled receptor (GPCR) signaling in the visual and nervous systems. Here, we identify R7BP, a novel neuronally expressed protein that binds R7-Gbeta5 complexes and shuttles them between the plasma membrane and nucleus. Regional expression of R7BP, Gbeta5, and R7 isoforms in brain is highly coincident. R7BP is palmitoylated near its COOH terminus, which targets the protein to the plasma membrane. Depalmitoylation of R7BP translocates R7BP-R7-Gbeta5 complexes from the plasma membrane to the nucleus. Compared with nonpalmitoylated R7BP, palmitoylated R7BP greatly augments the ability of RGS7 to attenuate GPCR-mediated G protein-regulated inward rectifying potassium channel activation. Thus, by controlling plasma membrane nuclear-shuttling of R7BP-R7-Gbeta5 complexes, reversible palmitoylation of R7BP provides a novel mechanism that regulates GPCR signaling and potentially transduces signals directly from the plasma membrane to the nucleus.
Drenan
Ryan M
RM
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Doupnik
Craig A
CA
Boyle
Maureen P
MP
Muglia
Louis J
LJ
Huettner
James E
JE
Linder
Maurine E
ME
Blumer
Kendall J
KJ
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D019308:Palmitic Acid / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D020710:RGS Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D044387:GTP-Binding Protein beta Subunits; C094668:Gnb5 protein, mouse; D008565:Membrane Proteins; D015221:Potassium Channels; C499440:R7BP protein, mouse; D020710:RGS Proteins; D043562:Receptors, G-Protein-Coupled; C492038:Rgs7 protein, mouse; D019308:Palmitic Acid