Insulin receptor regulates photoreceptor CNG channel activity

Author:

Gupta Vivek K.12,Rajala Ammaji12,Rajala Raju V. S.1342

Affiliation:

1. Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma;

2. Dean A. McGee Eye Institute, Oklahoma City, Oklahoma

3. Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma;

4. Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; and

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 Tyr498 and Tyr503 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.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology,Endocrinology, Diabetes and Metabolism

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