2013 Fiscal Year Final Research Report
Signaling and molecular mechanisms of myofibrillogenesis participating in muscle regeneration and muscle and cardiac hypertrophy
| Project/Area Number |
23300144
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurophysiology and muscle physiology
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| Research Institution | Chiba University |
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Principal Investigator |
ENDO Takeshi 千葉大学, 理学(系)研究科(研究院), 教授 (30194038)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKANO Kazunori 千葉大学, 大学院・融合科学研究科, 助教 (60466860)
TAKANO Haruko 千葉大学, 大学院・医学研究院, 振興会特別研究員 (40532891)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | シグナル伝達 / IGF-1シグナリング / 筋原線維 / アクチン線維 / N-WASP / サルコメア蛋白質 / 筋疾患 / 心肥大 |
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| Research Abstract |
This research project aimed to elucidate signaling and molecular mechanisms of myofibrillar actin filament formation. We found that N-WASP bound to the SH3 domain of nebulette (Nebt) in the Z bands of cardiac myofibrils. The Nebt-N-WASP complex nucleated actin to form actin filaments from the Z-bands. Furthermore, Lmod2 bound to N-terminal region of Nebt and seemed to extend short actin filaments preformed by the Nebt-N-WASP complex. GSK-3beta phosphorylated Nebt C-terminal region, N-WASP, and Lmod2, possibly resulting in their inactivation or degradation. Transverse aortic constriction caused pathological cardiac hypertrophy, fibrosis, and deterioration of cardiac function in mice. Administration of IGF-1 to mice ameliorated these symptoms, whereas that of an N-WASP inhibitor worsened them. Thus, actin filament formation induced by N-WASP activated by IGF-1 signaling is required for normal cardiac functions by interfering with pathological cardiac phenotypes.
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[Journal Article] DA-Raf-dependent inhibition of the Ras-ERK signaling pathway in type 2 alveolar epithelial cells controls alveolar formation2014
Author(s)
Watanabe-Takano, H., Takano, K., Sakamoto, A., Matsumoto, K., Tokuhisa, T., Endo, T., and Hatano M
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Journal Title
Proc. Natl. Acad. Sci. USA
Volume: 111(in press)
URL
Peer Reviewed
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[Journal Article] The nebulin SH3 domain is dispensable for normal skeletal muscle structure but is required for effective active load bearing in mouse2013
Author(s)
Yamamoto, D. L., Vitiello, C., Zhang, J., Gokhin, D. S., Castaldi, A., Coulis, G., Piaser, F., Filomena, M. C., Eggenhuizen, P. J., Kunderfranco, P., Camerini, S., Takano, K., Endo, T., Crescenzi, M., Luther, P., Lieber, R. L., Chen, J., and Bang, M.-L
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Journal Title
J. Cell Sci
Volume: 126
Pages: 5477-5489
DOI
Peer Reviewed
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[Journal Article] RhoD activated by fibroblast growth factor induces cytoneme-like cellular protrusions through mDia3C2012
Author(s)
Koizumi, K., Takano, K., Kaneyasu, A., Watanabe-Takano, H., Tokuda, E., Abe, T., Watanabe, N., Takenawa, T., and Endo, T
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Journal Title
Mol. Biol. Cell
Volume: 23
Pages: 4647- 4661
DOI
Peer Reviewed
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[Journal Article] Signal transduction of pregnenolone sulfate in insulinoma cells : activation of Egr-1 expression involving TRPM3, voltage-gated calcium channels, ERK, and ternary complex factors2011
Author(s)
Mayer, S. I., Müller, I., Mannebach, S., Endo, T., and Thiel, G
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Journal Title
J. Biol. Chem
Volume: 286
Pages: 10084-10096
DOI
Peer Reviewed
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