2006 Fiscal Year Final Research Report Summary
Analysis of the mechanism of septin polymerization and depolymerization
| Project/Area Number |
18370077
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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 |
Cell biology
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| Research Institution | Kyoto University |
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Principal Investigator |
KINOSHITA Makoto Kyoto University, Graduate School of Medicine, lecturer (30273460)
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| Project Period (FY) |
2006 – 2007
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| Keywords | biomolecule / protein / cell / tissue / brain / nervous system / cytoskeleton / reconstirution / live imaging / knockout mouse |
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| Research Abstract |
Microtubule and actin cytoskeleton provide infrastructure for neuronal and glial morphology and functions, whereas another ubiquitous nucleotide-binding cytoskeleton composed of septins is poorly characterized despite their abundance in the brain and implications in synaptic transmission and neurodegeneration. Here we find diverse submembranous septin clusters in vivo and analyze their dynamic properties and functions in vitro. Stereoscopic reconstruction of serial immunoelectron micrographs of the mouse brain reveals numerous septin clusters that contain brain-specific subunits. In the cerebellum, Sept4-containing septin heteropolymers cluster beneath concave membrane regions of Bergmann glial processes each surrounds a dendritic spine neck of a Purkinje cell, while Sept5-containing clusters preferentially underlie dendritic shafts up to spine bases in Purkinje cells. In the hippocampus, Sept3-containing clusters localize beneath mossy fiber terminals that intricately wrap around pyramidal cell dendrites. The unique distribution of septin clusters should reflect their as yet unidentified roles beneath specific extra/para-synaptic membrane domains in neurons and glia. As an in vitro approach to address this, we examine temporal properties of septins and related molecules underlying neuroblastoma cell membrane by fluorescence recovery after photobleaching (FRAP) analysis. The remodeling dynamics of cortical septin assembly is intrinsically slow, which is facilitated by actin turnover. While RNAi-mediated septin depletion does not significantly affect cortical actin dynamics, it enhances the diffusional mobilities of membrane proteins. Together, the submembranous septin clusters found in vivo may serve as scaffolds and/or diffusion barriers that biochemically tether and/or physically restrain a specific subset of membrane-proximal molecules for the functional compartmentalization of specialized membrane subdomains.
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[Journal Article] Sept4, a component of presynaptic scaffold and Lewy bodies, is required for the suppression of a-synuclein neurotoxicity2007
Author(s)
Ihara, M., Yamasaki, N., Hagiwara, A., Tomimoto, H., Kitano, A., Tanigaki, A., Hikawa, E., Noda, M., Takanashi, M., Mori, H., Hattori, N., Miyakawa,T., Kinoshita, M
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Loss of Sept4 exacerbates liver fibrosis through the dysregulation of hepatic stellate cells
Author(s)
Iwaisako, K., Hatano, E., Taura, K., Nakajima, A., Tada, M., Seo, S., Tamaki, N., Ikai, I., Uemoto, S., Kinoshita, M
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Journal Title
Journal of Hepatology (in press)
Description
「研究成果報告書概要(欧文)」より
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