caa a22 4500 606174672 CHVBK 20210128100739.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00018-014-1664-6 doi (NATIONALLICENCE)springer-10.1007/s00018-014-1664-6 Using siRNA to define functional interactions between melanopsin and multiple G Protein partners [Elektronische Daten] [Steven Hughes, Aarti Jagannath, Doron Hickey, Silvia Gatti, Matthew Wood, Stuart Peirson, Russell Foster, Mark Hankins] Melanopsin expressing photosensitiveretinal 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. The Author(s), 2014 Melanopsin nationallicence G protein nationallicence Phototransduction nationallicence Gene silencing nationallicence Pupilometry nationallicence Hughes Steven Nuffield Laboratory of Ophthalmology, University of Oxford, OX3 9DU, Oxford, UK aut Jagannath Aarti Nuffield Laboratory of Ophthalmology, University of Oxford, OX3 9DU, Oxford, UK aut Hickey Doron Nuffield Laboratory of Ophthalmology, University of Oxford, OX3 9DU, Oxford, UK aut Gatti Silvia F. Hoffman La Roche, RED Research and Development, CNS DTA, Basel, Switzerland aut Wood Matthew Department of Anatomy, Physiology and Genetics, University of Oxford, Le Gros Clark Building, South Parks Road, OX1 3QX, Oxford, UK aut Peirson Stuart Nuffield Laboratory of Ophthalmology, University of Oxford, OX3 9DU, Oxford, UK aut Foster Russell Nuffield Laboratory of Ophthalmology, University of Oxford, OX3 9DU, Oxford, UK aut Hankins Mark Nuffield Laboratory of Ophthalmology, University of Oxford, OX3 9DU, Oxford, UK aut Cellular and Molecular Life Sciences Springer Basel 72/1(2015-01-01), 165-179 1420-682X 72:1<165 2015 72 18 https://doi.org/10.1007/s00018-014-1664-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-014-1664-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hughes Steven Nuffield Laboratory of Ophthalmology, University of Oxford, OX3 9DU, Oxford, UK aut NATIONALLICENCE 700 1- Jagannath Aarti Nuffield Laboratory of Ophthalmology, University of Oxford, OX3 9DU, Oxford, UK aut NATIONALLICENCE 700 1- Hickey Doron Nuffield Laboratory of Ophthalmology, University of Oxford, OX3 9DU, Oxford, UK aut NATIONALLICENCE 700 1- Gatti Silvia F. Hoffman La Roche, RED Research and Development, CNS DTA, Basel, Switzerland aut NATIONALLICENCE 700 1- Wood Matthew Department of Anatomy, Physiology and Genetics, University of Oxford, Le Gros Clark Building, South Parks Road, OX1 3QX, Oxford, UK aut NATIONALLICENCE 700 1- Peirson Stuart Nuffield Laboratory of Ophthalmology, University of Oxford, OX3 9DU, Oxford, UK aut NATIONALLICENCE 700 1- Foster Russell Nuffield Laboratory of Ophthalmology, University of Oxford, OX3 9DU, Oxford, UK aut NATIONALLICENCE 700 1- Hankins Mark Nuffield Laboratory of Ophthalmology, University of Oxford, OX3 9DU, Oxford, UK aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/1(2015-01-01), 165-179 1420-682X 72:1<165 2015 72 18