TY - JOUR
T1 - Opn5L1 is a retinal receptor that behaves as a reverse and self-regenerating photoreceptor
AU - Sato, Keita
AU - Yamashita, Takahiro
AU - Ohuchi, Hideyo
AU - Takeuchi, Atsuko
AU - Gotoh, Hitoshi
AU - Ono, Katsuhiko
AU - Mizuno, Misao
AU - Mizutani, Yasuhisa
AU - Tomonari, Sayuri
AU - Sakai, Kazumi
AU - Imamoto, Yasushi
AU - Wada, Akimori
AU - Shichida, Yoshinori
N1 - Funding Information:
We thank Prof. R.S. Molday for the generous gift of a Rho1D4-producing hybridoma, Prof. S. Koike for HEK293T cell line, Prof. H. Niwa for pCAGGS vector, and The Institute for Amphibian Biology (Hiroshima University, Hiroshima, Japan) for X. tropicalis through the National Bio-Resource Project of the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT). We are also grateful to Prof. S. Noji and Ms. S. Fujita-Yanagibayashi for fruitful discussions, and Prof. B. Leonid, Prof. M. Kono, Dr. E. Nakajima, and Dr. T. Matsuyama for critical reading of our manuscript and invaluable comments. This work was supported by Grants-in-Aid for Scientific Research 25251036 and 16H02515 (to Y.S.) and 24115509 and 15H00812 (to T.Y.) from the Japanese Ministry of Education, Culture, Sports, Science and Technology, a grant from the Takeda Science Foundation (to T.Y.) and from Daiichi Sankyo Foundation of Life Science (to T.Y.) and CREST, JST JPMJCR1753 (to T.Y.)
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Most opsins are G protein-coupled receptors that utilize retinal both as a ligand and as a chromophore. Opsins' main established mechanism is light-triggered activation through retinal 11-cis-to-all-trans photoisomerization. Here we report a vertebrate non-visual opsin that functions as a Gi-coupled retinal receptor that is deactivated by light and can thermally self-regenerate. This opsin, Opn5L1, binds exclusively to all-trans-retinal. More interestingly, the light-induced deactivation through retinal trans-to-cis isomerization is followed by formation of a covalent adduct between retinal and a nearby cysteine, which breaks the retinal-conjugated double bond system, probably at the C11 position, resulting in thermal re-isomerization to all-trans-retinal. Thus, Opn5L1 acts as a reverse photoreceptor. We conclude that, like vertebrate rhodopsin, Opn5L1 is a unidirectional optical switch optimized from an ancestral bidirectional optical switch, such as invertebrate rhodopsin, to increase the S/N ratio of the signal transduction, although the direction of optimization is opposite to that of vertebrate rhodopsin.
AB - Most opsins are G protein-coupled receptors that utilize retinal both as a ligand and as a chromophore. Opsins' main established mechanism is light-triggered activation through retinal 11-cis-to-all-trans photoisomerization. Here we report a vertebrate non-visual opsin that functions as a Gi-coupled retinal receptor that is deactivated by light and can thermally self-regenerate. This opsin, Opn5L1, binds exclusively to all-trans-retinal. More interestingly, the light-induced deactivation through retinal trans-to-cis isomerization is followed by formation of a covalent adduct between retinal and a nearby cysteine, which breaks the retinal-conjugated double bond system, probably at the C11 position, resulting in thermal re-isomerization to all-trans-retinal. Thus, Opn5L1 acts as a reverse photoreceptor. We conclude that, like vertebrate rhodopsin, Opn5L1 is a unidirectional optical switch optimized from an ancestral bidirectional optical switch, such as invertebrate rhodopsin, to increase the S/N ratio of the signal transduction, although the direction of optimization is opposite to that of vertebrate rhodopsin.
UR - http://www.scopus.com/inward/record.url?scp=85044542277&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044542277&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-03603-3
DO - 10.1038/s41467-018-03603-3
M3 - Article
C2 - 29593298
AN - SCOPUS:85044542277
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1255
ER -