Photochemical Properties of Mammalian Melanopsin

Melanopsin is the photoreceptor molecule of intrinsically
photosensitive
retinal ganglion cells, which serve as the input for various nonvisual
behavior and physiological functions fundamental to organisms. The
retina, therefore, possess a melanopsin-based nonvisual system in
addition to the visual system based on the classical visual photoreceptor
molecules. To elucidate the molecular properties of melanopsin, we
have exogenously expressed mouse melanopsin in cultured cells. We
were able to obtain large amounts of purified mouse melanopsin and
conducted a comprehensive spectroscopic study of its photochemical
properties. Melanopsin has an absorption maximum at 467 nm, and it
converts to a meta intermediate having an absorption maximum at 476
nm. The melanopsin photoreaction is similar to that of squid rhodopsin,
exhibiting bistability that results in a photosteady mixture of a
resting state (melanopsin containing 11-cis-retinal)
and an excited state (metamelanopsin containing all-trans-retinal) upon sustained irradiation. The absorption coefficient
of melanopsin is 33000 ± 1000 M–1 cm–1, and its quantum yield of isomerization is 0.52; these values are
also typical of invertebrate bistable pigments. Thus, the nonvisual
system in the retina relies on a type of photoreceptor molecule different
from that of the visual system. Additionally, we found a new state
of melanopsin, containing 7-cis-retinal (extramelanopsin),
which forms readily upon long-wavelength irradiation (yellow to red
light) and photoconverts to metamelanopsin with short-wavelength (blue
light) irradiation. Although it is unclear whether extramelanopsin
would have any physiological role, it could potentially allow wavelength-dependent
regulation of melanopsin functions.