Journal
CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 72, Issue 1, Pages 165-179Publisher
SPRINGER BASEL AG
DOI: 10.1007/s00018-014-1664-6
Keywords
Melanopsin; G protein; Phototransduction; Gene silencing; Pupillometry
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Funding
- F. Hoffmann La Roche
- Wellcome Trust
- BBSRC [BB/I021086/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/I021086/1] Funding Source: researchfish
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Melanopsin expressing photosensitive retinal ganglion cells (pRGCs) represent a third class of ocular photoreceptors and mediate a range of non-image forming responses to light. Melanopsin is a G protein coupled receptor (GPCR) and existing data suggest that it employs a membrane bound signalling cascade involving Gnaq/11 type G proteins. However, to date the precise identity of the G alpha subunits involved in melanopsin phototransduction remains poorly defined. Here we show that Gnaq, Gna11 and Gna14 are highly co-expressed in pRGCs of the mouse retina. Furthermore, using RNAi based gene silencing we show that melanopsin can signal via Gnaq, Gna11 or Gna14 in vitro, and demonstrate that multiple members of the Gnaq/11 subfamily, including Gna14 and at least Gnaq or Gna11, can participate in melanopsin phototransduction in vivo and contribute to the pupillary light responses of mice lacking rod and cone photoreceptors. This diversity of G protein interactions suggests additional complexity in the melanopsin phototransduction cascade and may provide a basis for generating the diversity of light responses observed from pRGC subtypes.
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