Melanopsin-Encoded Response Properties of Intrinsically Photosensitive Retinal Ganglion Cells

Melanopsin photopigment expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs) plays a crucial role in the adaptation of mammals to their ambient light environment through both image-forming and non-image-forming visual responses. The ipRGCs are structurally and functionally distinct from classical rod/cone photoreceptors and have unique properties, including single-photon response, long response latency, photon integration over time, and slow deactivation. We discovered that amino acid sequence features of melanopsin protein contribute to the functional properties of the ipRGCs. Phosphorylation of a cluster of Ser/Thr residues in the C-terminal cytoplasmic region of melanopsin contributes to deactivation, which in turn determines response latency and threshold sensitivity of the ipRGCs. The poorly conserved region distal to the phosphorylation cluster inhibits phosphorylation's functional role, thereby constituting a unique delayed deactivation mechanism. Concerted action of both regions sustains responses to dim light, allows for the integration of light over time, and results in precise signal duration.