title: Melanopsin ganglion cells use a membrane-associated rhabdomeric phototransduction cascade.
abstract: Intrinsically photosensitive retinal ganglion cells (ipRGCs) are photoreceptors of the mammalian eye that drive pupillary responses, synchronization of circadian rhythms, and other reflexive responses to daylight. Melanopsin is the ipRGC photopigment, but the signaling cascade through which this invertebrate-like opsin triggers the photocurrent in these cells is unknown. Here, using patch-clamp recordings from dissociated ipRGCs in culture, we show that a membrane-associated phosphoinositide cascade lies at the heart of the ipRGC phototransduction mechanism, similar to the cascade in rhabdomeric photoreceptors of invertebrate eyes. When ipRGCs were illuminated, melanopsin activated a G protein of the G(q/11) class, stimulating the effector enzyme phospholipase C. The presence of these signaling components in ipRGCs was confirmed by single-cell RT-PCR and immunofluorescence. The photoresponse was fully functional in excised inside-out patches of ipRGC membrane, indicating that all core signaling components are within or tightly coupled to the plasma membrane. The striking similarity of phototransduction in ipRGCs and invertebrate rhabdomeric photoreceptors reinforces the emerging view that these cells have a common evolutionary origin.
authors.affiliation: Department of Neuroscience, Brown University, Providence, RI 02912, USA.
authors.forename: Dustin M
authors.initials: DM
authors.lastname: Graham
authors.forename: Kwoon Y
authors.initials: KY
authors.lastname: Wong
authors.forename: Peter
authors.initials: P
authors.lastname: Shapiro
authors.forename: Courtney
authors.initials: C
authors.lastname: Frederick
authors.forename: Kartik
authors.initials: K
authors.lastname: Pattabiraman
authors.forename: David M
authors.initials: DM
authors.lastname: Berson
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D004075:Diglycerides / Q000502:physiology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins / Q000502:physiology; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000502:physiology; D055537:Light Signal Transduction / Q000502:physiology*; D008297:Male; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017299:Rod Opsins / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology; D000099210:Melanopsin
chemical_list: D002118:Calcium; D004075:Diglycerides; D004533:Egtazic Acid; D004791:Enzyme Inhibitors; D019204:GTP-Binding Proteins; D006493:Heparin; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011493:Protein Kinase C; D017299:Rod Opsins; D019284:Thapsigargin; D000099210:Melanopsin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid