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R. L. Brown, M. F. Matos, N. Wettschureck, J. Zhang, P. R. Robinson, S. Offermanns, S. Hattar; G-protein Signaling in Melanopsin-containing Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5035.
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In addition to rod and cone photoreceptors, which mediate visual function, the retina contains a third photoreceptive cell - the intrinsically photosensitive retinal ganglion cell (ipRGC), which expresses the G-protein coupled receptor melanopsin (Opn4) and is primarily used for non-image forming responses to light. These cells project to brain centers that include the suprachiasmatic nuclei (SCN), the central circadian pacemaker, and the olivary pretectal nucleus (OPN), a relay nucleus involved in the pupillary light reflex (PLR). Despite intensive research over the past five years, little is conclusively known about the downstream effectors of activated melanopsin. Based on several lines of evidence, melanopsin is thought to use a member of the Gq family (q, 11, 14, or 15) as its cognate G protein in vivo.
We used traditional, as well as conditional, gene knockouts to eliminate several G proteins individually and in combination. To assess the function of the melanopsin-based signaling cascade, we used behavioral tests, such as the PLR and circadian photoentrainment, as well as single-cell patch-clamp recording from SCN-projecting RGCs.
Behavioral tests demonstrated that Gq/G11 double knockout animals have a defective PLR at both low and high light intensities. Gq/G11 DKO animals, however, seem to have normal circadian entrainment, and the single-cell light responses from SCN-projecting RGS are indistinguishable from wild-types.
In Gq/G11 DKO animals, melanopsin-based signaling appears intact in ipRGCs that project to the SCN and are involved in circadian entrainment, but impaired in ipRGCs that project to the OPN, which are involved in the PLR. These results suggest that ipRGCs projecting to different brain regions may use different G protein for signaling and/or targeting to the brain.
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