TY - JOUR
T1 - Farnesylation of retinal transducin underlies its translocation during light adaptation
AU - Kassai, Hidetoshi
AU - Aiba, Atsu
AU - Nakao, Kazuki
AU - Nakamura, Kenji
AU - Katsuki, Motoya
AU - Xiong, Wei Hong
AU - Yau, King Wai
AU - Imai, Hiroo
AU - Shichida, Yoshinori
AU - Satomi, Yoshinori
AU - Takao, Toshifumi
AU - Okano, Toshiyuki
AU - Fukada, Yoshitaka
N1 - Funding Information:
We thank Mr. Noritomo Tammitsu (Department of Biophysics, Graduate School of Science, Kyoto University) and Drs. Yoshiki Ueda and Yoshihito Honda (Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine) for helpful discussions about ERG recordings. We are grateful to Dr. Shinichi Aizawa (Center for Developmental Biology, RIKEN) for providing DT-A construct, Dr. Ken’ichi Hagiwara (Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases) for providing purified rat phosducin, and Drs. Naomasa Miki and Che-Hui Kuo (Department of Pharmacology, Osaka University Medical School) for providing phosducin antibody. We also thank anonymous reviewers for their valuable and constructive comments on the original version of this manuscript. This work was supported in part by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government (to Y.F.) and by a Human Frontiers Science Program grant (to Y.F.). W.-H.X. and K.-W.Y. were supported by a grant from the US National Eye Institute.
PY - 2005/8/18
Y1 - 2005/8/18
N2 - G proteins are posttranslationally modified by isoprenylation: either farnesylation or geranylgeranylation. The γ subunit of retinal transducin (Tα/Tβγ) is selectively farnesylated, and the farnesylation is required for light signaling mediated by transducin in rod cells. However, whether and how this selective isoprenylation regulates cellular functions remain poorly understood. Here we report that knockin mice expressing geranylgeranylated Tγ showed normal rod responses to dim flashes under dark-adapted conditions but exhibited impaired properties in light adaptation. Of note, geranylgeranylation of Tγ suppressed light-induced transition of Tβγ from membrane to cytosol, and also attenuated its light-dependent translocation from the outer segment to the inner region, an event contributing to retinal light adaptation. These results indicate that, while the farnesylation of transducin is interchangeable with the geranylgeranylation in terms of the light signaling, the selective farnesylation is important for visual sensitivity regulation by providing sufficient but not excessive membrane anchoring of Tβγ.
AB - G proteins are posttranslationally modified by isoprenylation: either farnesylation or geranylgeranylation. The γ subunit of retinal transducin (Tα/Tβγ) is selectively farnesylated, and the farnesylation is required for light signaling mediated by transducin in rod cells. However, whether and how this selective isoprenylation regulates cellular functions remain poorly understood. Here we report that knockin mice expressing geranylgeranylated Tγ showed normal rod responses to dim flashes under dark-adapted conditions but exhibited impaired properties in light adaptation. Of note, geranylgeranylation of Tγ suppressed light-induced transition of Tβγ from membrane to cytosol, and also attenuated its light-dependent translocation from the outer segment to the inner region, an event contributing to retinal light adaptation. These results indicate that, while the farnesylation of transducin is interchangeable with the geranylgeranylation in terms of the light signaling, the selective farnesylation is important for visual sensitivity regulation by providing sufficient but not excessive membrane anchoring of Tβγ.
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U2 - 10.1016/j.neuron.2005.07.025
DO - 10.1016/j.neuron.2005.07.025
M3 - Article
C2 - 16102536
AN - SCOPUS:23744480236
VL - 47
SP - 529
EP - 539
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 4
ER -