Rhodopsin-Regulated Grb14 Trafficking to Rod Outer Segments: Functional Role of Grb14 in Photoreceptors

Abstract

Growth factor receptor-bound protein 14 (Grb14) belongs to the Grb7 family. It is an adapter molecule, lacking any intrinsic enzyme activity, but mediates protein-protein and protein-lipid interactions. In photoreceptors, Grb14 undergoes a rhodopsin-dependent translocation from the inner segments to the outer segments. In photoreceptors, Grb14 undergoes a light-dependent tyrosine phosphorylation and protects the insulin receptor (IR) phosphorylation, which is neuroprotective. Outersegment- localized Grb14 also modulates the activity of the cyclic nucleotide gated (CNG) chancel. Thus, Grb14 plays a key role in receiving signals from rhodopsin, and translocating to outer segments, where it regulates IR and CNG channel activities. The present study supports the idea that rhodopsin regulates non-canonical signaling pathways in photoreceptor cells.

Keywords: CNG channel, Grb14, Insulin receptor, PTP1B, Rhodopsin, Rod outer segments, Tyrosine phosphorylation.

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