PMID:26320947

Citation	Jagannath, A, Hughes, S, Abdelgany, A, Pothecary, CA, Di Pretoro, S, Pires, SS, Vachtsevanos, A, Pilorz, V, Brown, LA, Hossbach, M, MacLaren, RE, Halford, S, Gatti, S, Hankins, MW, Wood, MJ, Foster, RG and Peirson, SN (2015) Isoforms of Melanopsin Mediate Different Behavioral Responses to Light. Curr. Biol. 25:2430-4
Abstract	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.
Links	PubMed PMC4580334 Online version:10.1016/j.cub.2015.07.071
Keywords	Alternative Splicing; Amino Acid Sequence; Animals; Base Sequence; Circadian Rhythm; Humans; Light; Mice/genetics; Mice/physiology; Molecular Sequence Data; Motor Activity; Perceptual Masking; Protein Isoforms/genetics; Protein Isoforms/metabolism; Pupil/physiology; Pupil/radiation effects; Rod Opsins/chemistry; Rod Opsins/genetics; Rod Opsins/metabolism; Sleep
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:OPN4	acts_upstream_of_or_within	GO:0043153: entrainment of circadian clock by photoperiod	ECO:0006050: anti-sense experiment evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:OPN4	acts_upstream_of_or_within	GO:0045938: positive regulation of circadian sleep/wake cycle, sleep	ECO:0006050: anti-sense experiment evidence used in manual assertion		P		Seeded From UniProt	complete

References

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