April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
Structure-function Analysis Of Mouse Melanopsin
Author Affiliations & Notes
  • Megumi Hatori
    Regulatory Biology, Salk Institute, La Jolla, California
  • Daniel Gibbs
    Regulatory Biology, Salk Institute, La Jolla, California
  • James Demas
    Physics, St. Olaf College, Northfield, Minnesota
  • Satchidananda Panda
    Regulatory Biology, Salk Institute, La Jolla, California
  • Footnotes
    Commercial Relationships  Megumi Hatori, None; Daniel Gibbs, None; James Demas, None; Satchidananda Panda, None
  • Footnotes
    Support  JSPS Fellowship, NIH Grant EY016807
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3457. doi:
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      Megumi Hatori, Daniel Gibbs, James Demas, Satchidananda Panda; Structure-function Analysis Of Mouse Melanopsin. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3457.

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

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Purpose: : Melanopsin is an opsin class of G-protein coupled receptor (GPCR) expressed in a small subset of retinal ganglion cells (RGCs) which are intrinsically photosensitive (ipRGCs or mRGCs). Melanopsin shares limited protein sequence homology within the opsin region with other opsins and has a long C-terminus region that does not share significant sequence homology with any other protein. Such limited sequence conservation in melanopsin has made it difficult to assess the structural determinants for its function. Therefore, we carried out a systematic structure-function study of melanopsin by targeted mutagenesis.

Methods: : We generated more than 100 different truncation and point mutants in mouse melanopsin. The expression constructs were transiently transfected into mammalian tissue culture cells and tested for protein expression, membrane targeting, light activation, photobleaching and interaction with beta arrestin. We also tested the role of the long C-terminus region in functional melanopsin expression by expressing mutant melanopsin in the mouse RGCs and measured photoresponses.

Results: : Several mutations in the opsin region of melanopsin affected expression and membrane localization, while truncations and point mutations in the C-terminus cytoplasmic region had little impact on overall expression. Several C-terminus truncations and point mutations defined a region that plays an important role in interaction with beta arrestins, potential activity dependent phosphorylation and photo bleaching. Expression of wild type or several mutant melanopsin in the mouse RGCs imparted photosensitivity, some with distinct response properties.

Conclusions: : The study identified several key structural features of melanopsin implicated in various aspects of its photoresponse properties.

Keywords: ganglion cells • circadian rhythms • photoreceptors 

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