Role of Rho- and Ca^<2+>-dependent signaling mechanisms in the regulation of neuronal actin cytoskeleton
| Project/Area Number |
17300116
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
BITO Haruhiko The University of Tokyo, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (00291964)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2006: ¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2005: ¥9,300,000 (Direct Cost: ¥9,300,000)
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| Keywords | brain and central nervous system / enzyme / gene / signal transduction / molecular biology / カルシウム / キナーゼ / 低分子量GTP結合蛋白質 / アクチン |
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| Research Abstract |
We here investigated the molecular signaling mechanisms underlying Rho- and Ca^<2+>-dependent modifications of neuronal actin cytoskeleton, as well as their physiological downstream consequences.
In order to identify a CaMK subtype involved, in dendrite formation and outgrowth, a systematic RNAi screening was carried out in a cortical neuronal culture system. No effect was seen on dendrites when CaMKIα, CaMKII, or CaMKIV were knocked down by shRNA. In contrast, shRNA of CLICK-III/CaMKIγ produced a robust decrease in dendritic growth, and this was accompanied with a drop in Rac activity. Further experiments suggested an essential role for a CLICK-III/CaMKIγ-STEF-Rac pathway during cortical dendritogenesis (Takemoto-Kimura et al., under revision)..
We next examined the potential impact of two CaMK-like kinases, CLICK-I/DCaMKL1 and CLICK-II/DCaMKL2, on dendritic morphology. Overexpression of splice variants containing an intact doublecortin domain revealed a strong bundling of microtubules, but little effect on actin cytoskeleton (Ohmae et al. J.Biol.Chem. 2006).
During the course of these studies, gene delivery protocols involving lipofection, adenoviral infection or gene gun were optimized. This led to striking discovery of spine morphological aberrance in PSD-95-mutant-expressing neurons (Nonaka et al., J.Neurosci. 2006). We also found that actin cytoskeleton and calcium dynamics may regulate cortactin or Shank localization in either hippocampal or Purkinje cell dendrites (Iki et al. Eur.J.Neurosci., 2005; Fuse et al. in preparation).
Finally, in collaboration with the Narumiya laboratory, we determined that Rho-mDia1-dependent regulation of actin cytoskeleton plays a critical role in the localization of Apc and Src complexes at distinct polarized positions in a migrating cell.
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Report
(3 results)
Research Products
(18 results)
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[Journal Article] Molecular identification and characterization of a family of kinases with homology to Ca2^<+>/calmodulin-dependent protein kinases I/IV2006
Author(s)
Ohmae S, Takemoto-Kimura S, Okamura M, Adachi-Morishima A, Nonaka M, Fuse T, Kida S, Tanji M, Furuyashiki T, Arakawa Y, Narumiya S, Okuno H, Bito H
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Journal Title
J.Biol.Chem. 281
Pages: 20427-20439
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Rho-mDia1 pathway regulates cell polarity and focal adhesion turnover in migrating cells through mobilizing APC and c-Src2006
Author(s)
Yamana N, Arakawa Y, Nishino T, Kurokawa K, Tanji M, Itoh RE, Monypenny J, Ishizaki T, Bito H, Nozaki K, Hashimoto K, Matsuda M, Narumiya S
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Journal Title
Mol.Cell Biol. 26
Pages: 6844-6858
Description
「研究成果報告書概要(欧文)」より
Related Report
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