| Project/Area Number |
08044267
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Nagoya University |
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Principal Investigator |
USUKURA Jiro NAGOYA UNIVERSITY. SCHOOL OF MEDICINE. ASSOCIATE PROFESSOR, 医学部, 助教授 (30143415)
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| Co-Investigator(Kenkyū-buntansha) |
OBATA Shuichi NAGOYA UNIVERSITY. SCHOOL OF MEDIHINE. ASSISTANT PROFESSOR, 医学部, 助手 (10204273)
HAGIWARA Masatoshi TOKYO MEDICAL DENTAL COLLEGE. ASSOCIATE PROFESSOR, 難治疾患研究所, 助教授 (10208423)
WAKABAYASHI Takashi NAGOYA UNIVERSITY. SCHOOL OF MEDICINE. PROFESSOR, 医学部, 教授 (00079998)
SHINOHARA Toshimichi HARVARD UNIVERSITY. SCHOOL OF MEDICINE. PROFESSOR, 医学部, 準教授
YAMAZAKI Akio WAYNE STATE UNIVERSITY. KRESGE EYE INSTITUTE. PROFESSOR, 医学部, 教授
MATSUMOTO Hi オクラホマ大学, 医学部, 準教授
SHINOHARA To ハーバード大学, 医学部, 準教授
YAMAZAKI Aki ウエインステート大学, 医学部, 準教授
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| Project Period (FY) |
1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | Phototransduction / Low angle rotary shadowing / Photoreceptor cell / Imaging / cGMP / PDE / Photoreception / Structural analysis |
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| Research Abstract |
The objective in this international cooperative research with Dr Akio Yamazaki, Kresge Eye Institute, Wayne State University, was to reveal morphological counterpart of the photo-transduction process in the vertebrate photoreceptor cells. In paticular, we aim to explore regulation of phosphodiesterase (PDE), one of the key components in phototransduction, by characterizing both functional and structural changes of PDE subunits and to elucidate new roles of PDE in visual signal transduction mechanism. In contrast to significant progress in understanding the flow of signals in phototransduction and the roles of each component in the flow of signals, the relationship between mechanism and structure of these components still remain unclear. Especially, the relationship in PDE subunits is unknown because of diffeculty of purification and expression of intact Pαβand lack of information about regulation of Pαβ-Pγ interactions. However, in this study, Pαβ-Pγ interactions were partially elucidated with new findings on the machanism of Pγ modifications and unexpected finding on the PDE role in the increase of cytoplasmic cGMP level in rod outer segments. Our recent development in the isolation and purification of bovine Pαβ with or without Pγ also made possible to observe the molecules under electron microscope. All types of PDE (αβγγ,αβγ,αβ) consisted basically of two crooked strands with characteristic shape that were arranged as making a ring. Theses two components faced each other relative to bending or twisting at about 30 - 60℃. Unfortunately, γ subunit was too small to be dected accurately by this technique. Nevertheless, suggestible structural changes induced by dislocation of Pγ from complete PDE were arrested as three dimentional shift of molecules in position.
At any rate, understanding molecular basis of Pαβ functional structure provided new insight into phototransduction mechanism.
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