title: Insulin receptor regulates photoreceptor CNG channel activity.
abstract: Photoreceptor cyclic nucleotide gated (CNG) channels are critical elements in phototransduction and light adaptation. Here we report that insulin receptor (IR), an integral membrane protein, directly phosphorylates the CNGA1 subunit of CNG channels that in turn affects the function of these channels negatively. The IR phosphorylates Tyr(498) and Tyr(503) residues on CNGA1 that are situated at the membrane-cytoplasmic interface. The IR tyrosine kinase activity is essential for the inhibition of CNG channel. To maintain the channels in an off state, it is necessary not only to have a precise balance of the cGMP levels but also to have a control on the cGMP sensitivity of the CNG channels itself. In this study, we observed that the channel opens at a lower concentration of cGMP in IR(-/-) mice. These studies suggest that IR regulates the modulation of CNG channel activity in vivo.
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Gupta
authors.forename: Ammaji
authors.initials: A
authors.lastname: Rajala
authors.forename: Raju V S
authors.initials: RV
authors.lastname: Rajala
mesh_terms: D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D010786:Photoreceptor Cells / Q000378:metabolism*; D010827:Physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk / Q000502:physiology*; D011972:Receptor, Insulin / Q000378:metabolism*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; C410467:insulin receptor tyrosine kinase; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin