Specificity of G protein-RGS protein recognition is regulated by affinity adapters.
RGS proteins regulate the duration of cell signaling by modulating the lifetime of activated G proteins. The specificity of RGS-G protein mutual recognition is critical for meeting unique timing requirements of numerous G protein-mediated pathways. Our study of two splice isoforms of RGS9 expressed in different types of neurons revealed a novel mechanism whereby this specificity is determined by specialized protein domains or subunits acting as affinity adapters. The long RGS9 isoform contains a C-terminal domain that provides high-affinity interaction with its target G protein. The lack of this domain in the short RGS9 isoform is compensated by the action of a G protein effector subunit that is structurally similar to this C-terminal domain. This allows the short isoform to specifically target the complex between the G protein and its effector. Thus, the specific timing needs of different signaling pathways can be accommodated by affinity adapters positioned at various pathway components.
Martemyanov
Kirill A
KA
Howe Laboratory of Ophthalmology, Harvard Medical School, The Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
Hopp
Johnathan A
JA
Arshavsky
Vadim Y
VY
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000378:metabolism; D002384:Catalysis; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D015870:Gene Expression; D051379:Mice; D009434:Neural Pathways; D009474:Neurons / Q000378:metabolism; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D020710:RGS Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014162:Transfection
D020033:Protein Isoforms; D020710:RGS Proteins; C116925:regulator of g-protein signaling 9; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C517438:Pde6b protein, mouse; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins