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Publication : Isoforms of Melanopsin Mediate Different Behavioral Responses to Light.

First Author  Jagannath A Year  2015
Journal  Curr Biol Volume  25
Issue  18 Pages  2430-4
PubMed ID  26320947 Mgi Jnum  J:252142
Mgi Id  MGI:5925970 Doi  10.1016/j.cub.2015.07.071
Citation  Jagannath A, et al. (2015) Isoforms of Melanopsin Mediate Different Behavioral Responses to Light. Curr Biol 25(18):2430-4
abstractText  Melanopsin (OPN4) is a retinal photopigment that mediates a wide range of non-image-forming (NIF) responses to light including circadian entrainment, sleep induction, the pupillary light response (PLR), and negative masking of locomotor behavior (the acute suppression of activity in response to light). How these diverse NIF responses can all be mediated by a single photopigment has remained a mystery. We reasoned that the alternative splicing of melanopsin could provide the basis for functionally distinct photopigments arising from a single gene. The murine melanopsin gene is indeed alternatively spliced, producing two distinct isoforms, a short (OPN4S) and a long (OPN4L) isoform, which differ only in their C terminus tails. Significantly, both isoforms form fully functional photopigments. Here, we show that different isoforms of OPN4 mediate different behavioral responses to light. By using RNAi-mediated silencing of each isoform in vivo, we demonstrated that the short isoform (OPN4S) mediates light-induced pupillary constriction, the long isoform (OPN4L) regulates negative masking, and both isoforms contribute to phase-shifting circadian rhythms of locomotor behavior and light-mediated sleep induction. These findings demonstrate that splice variants of a single receptor gene can regulate strikingly different behaviors.
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