Differential expression of two distinct functional isoforms of melanopsin (Opn4) in the mammalian retina.
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.
Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford OX3 9DU, United Kingdom.
Susana S
SS
Pires
Steven
S
Hughes
Michael
M
Turton
Zare
Z
Melyan
Stuart N
SN
Peirson
Lei
L
Zheng
Maria
M
Kosmaoglou
James
J
Bellingham
Michael E
ME
Cheetham
Robert J
RJ
Lucas
Russell G
RG
Foster
Mark W
MW
Hankins
Stephanie
S
Halford
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D012160:Retina / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D017299:Rod Opsins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D000099210:Melanopsin
D020033:Protein Isoforms; D017299:Rod Opsins; D000099210:Melanopsin