PMID:19793992

Citation	Pires, SS, Hughes, S, Turton, M, Melyan, Z, Peirson, SN, Zheng, L, Kosmaoglou, M, Bellingham, J, Cheetham, ME, Lucas, RJ, Foster, RG, Hankins, MW and Halford, S (2009) Differential expression of two distinct functional isoforms of melanopsin (Opn4) in the mammalian retina. J. Neurosci. 29:12332-42
Abstract	Melanopsin is the photopigment that confers photosensitivity to a subset of retinal ganglion cells (pRGCs) that regulate many non-image-forming tasks such as the detection of light for circadian entrainment. Recent studies have begun to subdivide the pRGCs on the basis of morphology and function, but the origin of these differences is not yet fully understood. Here we report the identification of two isoforms of melanopsin from the mouse Opn4 locus, a previously described long isoform (Opn4L) and a novel short isoform (Opn4S) that more closely resembles the sequence and structure of rat and human melanopsins. Both isoforms, Opn4L and Opn4S, are expressed in the ganglion cell layer of the retina, traffic to the plasma membrane and form a functional photopigment in vitro. Quantitative PCR revealed that Opn4S is 40 times more abundant than Opn4L. The two variants encode predicted proteins of 521 and 466 aa and only differ in the length of their C-terminal tails. Antibodies raised to isoform-specific epitopes identified two discrete populations of melanopsin-expressing RGCs, those that coexpress Opn4L and Opn4S and those that express Opn4L only. Recent evidence suggests that pRGCs show a range of anatomical subtypes, which may reflect the functional diversity reported for mouse Opn4-mediated light responses. The distinct isoforms of Opn4 described in this study provide a potential molecular basis for generating this diversity, and it seems likely that their differential expression plays a role in generating the variety of pRGC light responses found in the mammalian retina.
Links	PubMed PMC2802713 Online version:10.1523/JNEUROSCI.2036-09.2009
Keywords	Amino Acid Sequence; Animals; Base Sequence; Cells, Cultured; Gene Expression Regulation; Humans; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Molecular Sequence Data; Protein Isoforms/biosynthesis; Protein Isoforms/chemistry; Protein Isoforms/genetics; Protein Transport/genetics; Rats; Retina/chemistry; Retina/metabolism; Retina/physiology; Rod Opsins/biosynthesis; Rod Opsins/chemistry; Rod Opsins/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:OPN4	part_of	GO:0005886: plasma membrane	ECO:0000314: direct assay evidence used in manual assertion		C	part_of:(CL:0000740)	Seeded From UniProt	complete
MOUSE:OPN4	enables	GO:0008020: G protein-coupled photoreceptor activity	ECO:0000314: direct assay evidence used in manual assertion		F	occurs_in:(CL:0000740)	Seeded From UniProt	complete
MOUSE:OPN4	acts_upstream_of_or_within	GO:0016056: rhodopsin mediated signaling pathway	ECO:0000314: direct assay evidence used in manual assertion		P	occurs_in:(CL:0000740)	Seeded From UniProt	complete

References

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