title: Using siRNA to define functional interactions between melanopsin and multiple G Protein partners.
abstract: 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 Gα 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.
authors: Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, OX3 9DU, UK.
authors: Steven
authors: S
authors: Hughes
authors: Aarti
authors: A
authors: Jagannath
authors: Doron
authors: D
authors: Hickey
authors: Silvia
authors: S
authors: Gatti
authors: Matthew
authors: M
authors: Wood
authors: Stuart N
authors: SN
authors: Peirson
authors: Russell G
authors: RG
authors: Foster
authors: Mark W
authors: MW
authors: Hankins
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D044385:GTP-Binding Protein alpha Subunits / Q000037:antagonists & inhibitors / Q000502:physiology*; D007124:Immunoenzyme Techniques; D019426:Integrases / Q000378:metabolism; D008027:Light; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010775:Photic Stimulation; D011680:Pupil / Q000502:physiology* / Q000528:radiation effects; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017299:Rod Opsins / Q000037:antagonists & inhibitors / Q000502:physiology*; D000099210:Melanopsin
chemical_list: D002118:Calcium; D044385:GTP-Binding Protein alpha Subunits; D019426:Integrases; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017299:Rod Opsins; D000099210:Melanopsin; C045073:Cre recombinase