2007 Fiscal Year Final Research Report Summary
Neuronal polarization by a diffusion barrier at the axon initial segment
| Project/Area Number |
18500254
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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 |
Neuroscience in general
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
NISHIMURA Kazunari Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Organization for Medical Research, Tokyo Metropolitan Institute for Neuroscience, Research Scientist (90321794)
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| Project Period (FY) |
2006 – 2007
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| Keywords | neuronal polarity / diffusion barrier / axon initial segment / optical tweezers / cytoskeleton / L1CAM / glycosaminoglycan |
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| Research Abstract |
Morphology of polarized neurons consists of two types of domains, axon and somatodendrite, that express distinct sets of molecules required for physiological function. Since axon specification is remodeled in dissociated hippocampal neurons after plating in vitro, the establishment of neuronal polarity is independent on obvious polarity cues in extracellular milieu. The nascent axon is triggered by intracellular positive feedback loop of the signal molecules at one of the immature neurites. Following the cell-autonomous axon-specification, either axon or somatodendrite specific molecules are subcellularly distributed. Accordingly, major questions for fully understanding the mechanisms are how one of the immature neurites is selected to become the nascent axon, and how lateral diffusion of membrane molecules are impeded on the cell surface between polarized axon and soma. This research project revealed that intracellular localization of membrane cytoskeletons, both ankyrinG and betaIV-s
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pectrin, forms a diffusion barrier against the lateral mobility of axon specific LI cell adhesion molecule (L1CAM) at the axon initial segment between axon and soma. The barrier activity might depend on direct interaction of L1CAM with ankyrinG rather than on steric hindrance by other transmembrane proteins culusterd at the axon initial segment. Besides demonstrating the diffusion barrier, this research project revealed that extracellular glycosaminoglycans (GAGs) regulate axon-specification during the quite early stage of neuronal polarization. A certain type of highly sulfate GAG locally clusters around soma of hippocampal neurons just after dissociation, often localizes in a single neurite of the unpolarized neurons, and then distinctly localizes in axon after neuronal polarization. Enzymatic degradation of the GAG brings about formation of multiple axonal neurons, but nonsignificantly effects on elongating axons in total length. These findings suggest that neurons could cell-autonomously create obvious polarity cues in extracellular milieu for axon specification, and maintain the molecular distribution in proper domains by intracellular components after polarization. Less
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