June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Molecular Analysis of the Visual Pigment Melanopsin Reveals Unique Regulation of Receptor Activation, Desensitization, & Resensitization
Author Affiliations & Notes
  • Juan Valdez-Lopez
    Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland, United States
  • Evan Cameron
    Stanford University, Stanford, California, United States
  • Haya AlGrain
    Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland, United States
  • Olanike Awotunde
    Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland, United States
  • Jair Flores
    Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland, United States
  • Meheret Gebreegziabher
    Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland, United States
  • Phyllis Robinson
    Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Juan Valdez-Lopez, None; Evan Cameron, None; Haya AlGrain, None; Olanike Awotunde, None; Jair Flores, None; Meheret Gebreegziabher, None; Phyllis Robinson, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4147. doi:
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      Juan Valdez-Lopez, Evan Cameron, Haya AlGrain, Olanike Awotunde, Jair Flores, Meheret Gebreegziabher, Phyllis Robinson; Molecular Analysis of the Visual Pigment Melanopsin Reveals Unique Regulation of Receptor Activation, Desensitization, & Resensitization. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4147.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Melanopsin is a unique visual pigment expressed in a small subset of retinal ganglion cells in the mammalian retina, and is involved in non-image forming tasks such as circadian photoentrainment and pupil constriction. Data from both in vitro electrophysiology and calcium imaging assays, suggests that the activation kinetics of the melanopsin phototransduction cascade are sluggish, and the response has a unique sustained property in response to light, unlike the transient rod and cone responses. While several key players of melanopsin’s signaling cascade have been described (such as melanopsin’s coupling to GRKs & β-arrestins), there are additional signaling molecules that remain to be elucidated. First, we aim to describe the phosphorylation profile of melanopsin’s long C-terminus tail, which we hypothesize is contributing significantly to both receptor activation and deactivation. Second, we hypothesize that melanopsin interacts with a serine/threonine phosphatase, specifically, of the protein phosphatase family, and this interaction is important for resensitization of the receptor.

Methods : We aim to test the first hypothesis through mutagenesis of melanopsin’s gene, expression in HEK293 cells, and in vitro calcium imaging to measure signaling kinetics. To test the second hypothesis, will perform RT-PCR, immunohistochemistry, and protein interaction assays using retinal samples.

Results : We have found that there are six serines and threonines between residues 385 and 396 on the C-terminus that are required for signaling deactivation, and six additional serines and threonines in either proximal or distal direction that are needed for complete signaling deactivation. Additionally, we have evidence suggesting phosphorylation of the proximal C-terminus plays a role in receptor activation, possibly involving an important tyrosine residue (Y382). Finally, we have found diverse expression of protein phosphatases (subclasses 1-5) within the murine retina, and are beginning to explore which one of these interact with melanopsin.

Conclusions : We present these findings as contributors to melanopsin’s unique signaling properties within the mammalian retina.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

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