Addition of human melanopsin renders mammalian cells photoresponsive


A small number of mammalian retinal ganglion cells act as photoreceptors for regulating certain non-image forming photoresponses1,2,3,4,5,6,7,8,9,10. These intrinsically photosensitive retinal ganglion cells express the putative photopigment melanopsin11,12,13. Ablation of the melanopsin gene renders these cells insensitive to light14; 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.

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Figure 1: Expression of human melanopsin renders Neuro-2a cells light-sensitive.
Figure 2: Melanopsin uses cis-isoforms of retinaldehyde.
Figure 3: Spectral sensitivity.
Figure 4: The phototransduction cascade in melanopsin-expressing cells loaded with 9-cis-retinaldehyde.


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This work was supported by a Wellcome Trust Showcase Award (M.W.H. and R.J.L.) and in part by the BBSRC (R.J.L.) and NSBRI through NASA NCC 9-58 (R.J.L. and R. Foster). We are grateful to R.K. Crouch for the gift of 11-cis retinaldehyde, to R. Douglas for scientific discussions and comments on the manuscript, and to K. Wells for help and advice with cell culture.

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Correspondence to R. J. Lucas or M. W. Hankins.

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The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Figure 1

Opsin gene expression in Neuro-2a cells by RT-PCR. (PDF 260 kb)

Supplementary Figure 2

Detection of melanopsin and EGFP proteins in Neuro-2a cells by western blot. (PDF 596 kb)

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Melyan, Z., Tarttelin, E., Bellingham, J. et al. Addition of human melanopsin renders mammalian cells photoresponsive. Nature 433, 741–745 (2005).

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