2004 Fiscal Year Final Research Report Summary
Functional analysis of calcineurin-mediated signalling pathways using fission yeast as a model organism
| Project/Area Number |
14580698
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Kinki University (2004)
Kobe University (2002-2003) |
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Principal Investigator |
SUGIURA Reiko Kinki University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90294206)
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| Co-Investigator(Kenkyū-buntansha) |
KUNO Takayoshi Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50144564)
SHUNTOH Hisato Kobe Gakuin University, Faculty of rehabilitation, Professor, 医療福祉学部, 教授 (70206259)
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| Project Period (FY) |
2002 – 2004
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| Keywords | immunosuppressant / fission yeast / phosphorylation / cytokinesis / membrane trafficking / RNA-binding protein / MAP kinase |
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| Research Abstract |
Calcineurin (protein phosphatase 2B), the only serine/threonine phosphatase under the control of Ca2+/calmodulin, is an important mediator in signal transmission, connecting the Ca2+-dependent signalling to a wide variety of cellular responses. Calcineurin is an in vivo target of the immunosuppressant drug FK506 in fission yeast, and inhibition of calcineurin activity by gene disruption or by the addition of FK506 to the media does not affect the vegetative growth of fission yeast. We performed a genetic screen to search for the mutations that show sensitivity to the immunosuppressive drug FK506, and identified eight complementation groups. We identified PI4P5K Ypt3 small GTPase, subunits of clathrin-adaptor complex and demonstrated that these molecules and calcineurin share an essential function in cellular events such as cytokinesis, cell integrity and membrane trafficking. We also identified a downstream target of calcinerin ; Prz1, a zinc finger-type transcription factor. Prz1 was shown to be dephosphorylated by calcineurin and its transcriptional activity was also under the control of calcineurin-mediated signalling. Another approach to identify molecules that functionally interact with calcineurin signalling utilizes our discovery that calcineurin and the Pmk1 MAPK signalling function antagonistically in the Cl- homeostasis of fission yeast. Using this approach, we identified pmp1+ encoding MAPK phosphatase, pek1+ encoding MAPK kinase, and rnc1+, encoding an RNA-bindign protein. We also demonstrated that Pmp1 dephosphorylates and inactivates Pmk1, thereby negatively regulates Pmk1 siganlling. Rnc1 is a KH-type RNA-binding protein that binds and stabilizes the Pmp1 mRNA, thus acting as a negative feedback regulator of MAPK signalling.
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Research Products
(19 results)
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[Journal Article] Pmrl, a P-type ATPase, and Pdt1, an Nramp Homolog, Cooperatively Regulate Cell Morphogenesis in Fission Yeast : The Importance of Mn2+ Homeostasis.2004
Author(s)
Maeda-T, Sugiura-R, Kita-A, Saito-M, Deng-L, He-Y, Lu-Y, Fujita-Y, Takegawa-K, Shuntoh-H, Kuno-T
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Journal Title
Genes-Cells 9(1)
Pages: 71-82
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Loss of Apm1, the AP-1 Clathrin-Adaptor mu1 Subunit, Causes Distinct Phenotypes and Synthetic Lethality with Calcineurin Deletion in Fission Yeast2004
Author(s)
Kita A, Sugiura R, Shoji H, He Y, Deng L, Lu Y, Sio SO, Takegawa K, Sakaue M, Shuntoh H, Kuno T
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Journal Title
Mol Biol Cell. 15(6) Jun
Pages: 2920-2931
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Pmr1, a P-type ATPase, and Pdt1, an Nramp Homolog, Cooperatively Regulate Cell Morphogenesis in Fission Yeast : The Importance of Mn2+ Homeostasis.2004
Author(s)
Maeda-T, Sugiura-R, Kita-A, Saito-M, Deng-L, He-Y, Lu-Y, Fujita-Y, Takegawa-K, Shuntoh-H, Kuno-T
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Journal Title
Genes-Cells 9(1) Jan
Pages: 71-82
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Role of the Rab GTP-binding protein Ypt3 in the fission yeast exocytic pathway, and its connection to calcineurin function.2002
Author(s)
Cheng-H, Sugiura-R, Wu-W, Fujita-M, Lu-Y, Sio-SO, Kawai-R, Takegawa-K, Shuntoh-H, Kuno-T
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Journal Title
Mol-Biol-Cell 13(6)
Pages: 2963-2976
Description
「研究成果報告書概要(和文)」より
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