Melanopsin Forms a Functional Short-Wavelength Photopigment

Biochemistry. 2003 Nov 11;42(44):12734-8. doi: 10.1021/bi035418z.

Abstract

Recently, melanopsin has emerged as the leading candidate for the elusive photopigment of the mammalian circadian system. This novel opsin-like protein is expressed in retinal ganglion cells that form the retinohypothalamic tract, a neuronal connection between the retina and the suprachiasmatic nucleus. These hypothalamic structures contain the circadian pacemaker, which generates daily rhythms in physiology and behavior. In mammals, proper synchronization of these rhythms to the environmental light-dark cycle requires retinal input. Surprisingly, rod and cone photoreceptors are not required. Instead, the melanopsin-containing ganglion cells are intrinsically sensitive to light, perhaps responding via a melanopsin-based signaling pathway. To test this hypothesis, we have characterized melanopsin following heterologous expression in COS cells. We found that melanopsin absorbed maximally at 424 nm after reconstitution with 11-cis-retinal. Furthermore, melanopsin activated the photoreceptor G-protein, transducin, in a light-dependent manner. In agreement with the measured absorbance spectrum, melanopsin was most efficiently excited by blue light (420-440 nm). In contrast, published action spectra suggest that the photopigment underlying the intrinsic light sensitivity of SCN-projecting RGCs has an absorption maximum near 484 nm. In summary, our experiments constitute the first direct demonstration that melanopsin forms a photopigment capable of activating a G-protein, but its spectral properties are not consistent with the action spectrum for circadian entrainment.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • Cattle
  • Chlorocebus aethiops
  • Light
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Photoperiod
  • Retinal Ganglion Cells / chemistry
  • Retinal Ganglion Cells / physiology
  • Rod Opsins / genetics
  • Rod Opsins / isolation & purification*
  • Rod Opsins / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Spectrophotometry
  • Transducin / chemistry
  • Transducin / metabolism
  • Transfection
  • cis-trans-Isomerases / chemistry
  • cis-trans-Isomerases / genetics
  • cis-trans-Isomerases / physiology

Substances

  • Rod Opsins
  • melanopsin
  • Transducin
  • cis-trans-Isomerases