| First Author | Xu Y | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 20940 | PubMed ID | 26883481 |
| Mgi Jnum | J:391307 | Mgi Id | MGI:6215741 |
| Doi | 10.1038/srep20940 | Citation | Xu Y, et al. (2016) The TRPM1 channel in ON-bipolar cells is gated by both the alpha and the betagamma subunits of the G-protein Go. Sci Rep 6:20940 |
| abstractText | Transmission from photoreceptors to ON bipolar cells in mammalian retina is mediated by a sign-inverting cascade. Upon binding glutamate, the metabotropic glutamate receptor mGluR6 activates the heterotrimeric G-protein Galphaobeta3gamma13, and this leads to closure of the TRPM1 channel (melastatin). TRPM1 is thought to be constitutively open, but the mechanism that leads to its closure is unclear. We investigated this question in mouse rod bipolar cells by dialyzing reagents that modify the activity of either Galphao or Gbetagamma and then observing their effects on the basal holding current. After opening the TRPM1 channels with light, a constitutively active mutant of Galphao closed the channel, but wild-type Galphao did not. After closing the channels by dark adaptation, phosducin or inactive Galphao (both sequester Gbetagamma) opened the channel while the active mutant of Galphao did not. Co-immunoprecipitation showed that TRPM1 interacts with Gbeta3 and with the active and inactive forms of Galphao. Furthermore, bioluminescent energy transfer assays indicated that while Galphao interacts with both the N- and the C- termini of TRPM1, Gbetagamma interacts only with the N-terminus. Our physiological and biochemical results suggest that both Galphao and Gbetagamma bind TRPM1 channels and cooperate to close them. |
