Addition of human melanopsin renders mammalian cells photoresponsive

Nature. 2005 Feb 17;433(7027):741-5. doi: 10.1038/nature03344. Epub 2005 Jan 26.


A small number of mammalian retinal ganglion cells act as photoreceptors for regulating certain non-image forming photoresponses. These intrinsically photosensitive retinal ganglion cells express the putative photopigment melanopsin. Ablation of the melanopsin gene renders these cells insensitive to light; however, the precise role of melanopsin in supporting cellular photosensitivity is unconfirmed. Here we show that heterologous expression of human melanopsin in a mouse paraneuronal cell line (Neuro-2a) is sufficient to render these cells photoreceptive. Under such conditions, melanopsin acts as a sensory photopigment, coupled to a native ion channel via a G-protein signalling cascade, to drive physiological light detection. The melanopsin photoresponse relies on the presence of cis-isoforms of retinaldehyde and is selectively sensitive to short-wavelength light. We also present evidence to show that melanopsin functions as a bistable pigment in this system, having an intrinsic photoisomerase regeneration function that is chromatically shifted to longer wavelengths.

Publication types

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

MeSH terms

  • Animals
  • Calcium Signaling / radiation effects
  • Cell Line
  • Cyclic GMP / metabolism
  • Gene Expression
  • Heterotrimeric GTP-Binding Proteins / antagonists & inhibitors
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Humans
  • Light Signal Transduction / radiation effects*
  • Light*
  • Mice
  • Neurons / metabolism
  • Neurons / radiation effects*
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Retinaldehyde / chemistry
  • Retinaldehyde / metabolism
  • Rod Opsins / genetics
  • Rod Opsins / metabolism*


  • Protein Isoforms
  • Rod Opsins
  • melanopsin
  • Heterotrimeric GTP-Binding Proteins
  • Cyclic GMP
  • Retinaldehyde