Regulation of type V adenylate cyclase by Ric8a, a guanine nucleotide exchange factor.
In the present study, we demonstrate that AC5 (type V adenylate cyclase) interacts with Ric8a through directly interacting at its N-terminus. Ric8a was shown to be a GEF (guanine nucleotide exchange factor) for several alpha subunits of heterotrimeric GTP binding proteins (Galpha proteins) in vitro. Selective Galpha targets of Ric8a have not yet been revealed in vivo. An interaction between AC5 and Ric8a was verified by pull-down assays, co-immunoprecipitation analyses, and co-localization in the brain. Expression of Ric8a selectively suppressed AC5 activity. Treating cells with pertussis toxin or expressing a dominant negative Galphai mutant abolished the suppressive effect of Ric8a, suggesting that interaction between the N-terminus of AC5 and a GEF (Ric8a) provides a novel pathway to fine-tune AC5 activity via a Galphai-mediated pathway.
Wang
Shyi-Chyi
SC
Institute of Life Sciences, National Defence Medical Center, Taipei 104, Taiwan.
Lai
Hsing-Lin
HL
Chiu
Yi-Ting
YT
Ou
Ren
R
Huang
Chuen-Lin
CL
Chern
Yijuang
Y
D000262:Adenylyl Cyclases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D047468:Immunoprecipitation; D007527:Isoenzymes / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D011485:Protein Binding; D011817:Rabbits; D015398:Signal Transduction; D014162:Transfection
D020662:Guanine Nucleotide Exchange Factors; D007074:Immunoglobulin G; D007527:Isoenzymes; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V