Spinophilin inhibits the binding of RGS8 to M1-mAChR but enhances the regulatory function of RGS8.
We showed previously that RGS8 directly binds to the third intracellular loop (i3L) of the M1 muscarinic acetylcholine receptor using the sequence MPRR at the N-terminus of RGS8 and specifically inhibits signal transduction. Here, we identified spinophilin (SPL) as an RGS8-interacting protein. We found that the SPL-binding site of RGS8 is the MPRR sequence, and the M1 receptor and SPL compete for binding to RGS8. However, we also observed that the expression of SPL significantly enhances the inhibitory function of RGS8, and that SPL can bind to the M1 receptor, demonstrating the indirect binding of RGS8 to the M1 receptor through SPL for an efficient regulatory function.
Department of Bio-Science, Faculty of Bio-Science, Nagahama Institute of Bio-Science and Technology, Nagahama-shi, Shiga, Japan.
Seiji
S
Fujii
Ginko
G
Yamazoe
Masayuki
M
Itoh
Yoshihiro
Y
Kubo
Osamu
O
Saitoh
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009865:Oocytes; D020710:RGS Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D014981:Xenopus; D000099273:Neurabins
D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D020710:RGS Proteins; D043643:Receptor, Muscarinic M1; D000099273:Neurabins; C116924:RGS8 protein, human