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Publication : Cyclic-Nucleotide- and HCN-Channel-Mediated Phototransduction in Intrinsically Photosensitive Retinal Ganglion Cells.

First Author  Jiang Z Year  2018
Journal  Cell Volume  175
Issue  3 Pages  652-664.e12
PubMed ID  30270038 Mgi Jnum  J:267411
Mgi Id  MGI:6259254 Doi  10.1016/j.cell.2018.08.055
Citation  Jiang Z, et al. (2018) Cyclic-Nucleotide- and HCN-Channel-Mediated Phototransduction in Intrinsically Photosensitive Retinal Ganglion Cells. Cell 175(3):652-664.e12
abstractText  Non-image-forming vision in mammals is mediated primarily by melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs). In mouse M1-ipRGCs, by far the best-studied subtype, melanopsin activates PLCbeta4 (phospholipase C-beta4) to open TRPC6,7 channels, mechanistically similar to phototransduction in fly rhabdomeric (microvillous) photoreceptors. We report here that, surprisingly, mouse M4-ipRGCs rely on a different and hitherto undescribed melanopsin-driven, ciliary phototransduction mechanism involving cyclic nucleotide as the second messenger and HCN channels rather than CNG channels as the ion channel for phototransduction. Even more surprisingly, within an individual mouse M2-ipRGC, this HCN-channel-dependent, ciliary phototransduction pathway operates in parallel with the TRPC6,7-dependent rhabdomeric pathway. These findings reveal a complex heterogeneity in phototransduction among ipRGCs and, more importantly, break a general dogma about segregation of the two phototransduction motifs, likely with strong evolutionary implications.
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