The roles of neurofibromin in neuronal morphogenesis
博士 === 國立陽明大學 === 生命科學暨基因體科學研究所 === 96 === Neurons are highly polarized cells comprised single axon, multiple dendrites, and numerous dendritic spines. This unique morphology is important for neural functions. Neurofibromin, a tumor suppressor protein down regulating Ras activity and activating aden...
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ndltd-TW-096YM0051050052015-10-13T13:51:29Z http://ndltd.ncl.edu.tw/handle/63383732737458127438 The roles of neurofibromin in neuronal morphogenesis 神經纖維瘤蛋白對神經細胞型態發生之角色探討 Yi-Ling Lin 林怡伶 博士 國立陽明大學 生命科學暨基因體科學研究所 96 Neurons are highly polarized cells comprised single axon, multiple dendrites, and numerous dendritic spines. This unique morphology is important for neural functions. Neurofibromin, a tumor suppressor protein down regulating Ras activity and activating adenylate cyclase, regulates neurite outgrowth implying a potential role of neurofibromin in neuronal morphogenesis. By investigating the roles of neurofibromin-interacting proteins syndecan-2, VCP, and CRMP-2, the involvement of neurofibromin in neuronal morphogenesis was revealed. Syndecan-2 induces morphological change in various cell types. In neurons, syndecan-2 promotes spine formation via inducing filopodia formation. Here, a novel signaling pathway was revealed. Neurofibromin acted down stream of syndecan-2 to activate adenylate cyclase-PKA-Ena/VASP pathway and thus promotes filopodia formation. VCP, a molecule with multiple functions, mediates membrane fusion. It was shown that the interaction between neurofibromin and VCP is also required for spinogenesis by probably regulating membrane fusion. In addition to spinogenesis, neurofibromin is also involved in dendrite formation. Under the control of syndecan-2, neurofibromin regulated dendrite outgrowth by both PKA and VCP pathways. Finally, CRMP-2, a highly phosphorylated protein, is involved in axon outgrowth. CDK5 phosphorylated CRMP-2 leads to growth cone collapse. Neurofibromin interacted with CRMP-2 in a CDK5-dependent manner, suggesting that neurofibromin also plays a role in axonal outgrowth. In conclusion, neurofibromin regulates neuronal morphogenesis, which may account for neurological defects of NF1 patients. Yi-Ping Hsueh 薛一蘋 2008 學位論文 ; thesis 79 en_US |
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博士 === 國立陽明大學 === 生命科學暨基因體科學研究所 === 96 === Neurons are highly polarized cells comprised single axon, multiple dendrites, and numerous dendritic spines. This unique morphology is important for neural functions. Neurofibromin, a tumor suppressor protein down regulating Ras activity and activating adenylate cyclase, regulates neurite outgrowth implying a potential role of neurofibromin in neuronal morphogenesis. By investigating the roles of neurofibromin-interacting proteins syndecan-2, VCP, and CRMP-2, the involvement of neurofibromin in neuronal morphogenesis was revealed.
Syndecan-2 induces morphological change in various cell types. In neurons, syndecan-2 promotes spine formation via inducing filopodia formation. Here, a novel signaling pathway was revealed. Neurofibromin acted down stream of syndecan-2 to activate adenylate cyclase-PKA-Ena/VASP pathway and thus promotes filopodia formation. VCP, a molecule with multiple functions, mediates membrane fusion. It was shown that the interaction between neurofibromin and VCP is also required for spinogenesis by probably regulating membrane fusion. In addition to spinogenesis, neurofibromin is also involved in dendrite formation. Under the control of syndecan-2, neurofibromin regulated dendrite outgrowth by both PKA and VCP pathways. Finally, CRMP-2, a highly phosphorylated protein, is involved in axon outgrowth. CDK5 phosphorylated CRMP-2 leads to growth cone collapse. Neurofibromin interacted with CRMP-2 in a CDK5-dependent manner, suggesting that neurofibromin also plays a role in axonal outgrowth.
In conclusion, neurofibromin regulates neuronal morphogenesis, which may account for neurological defects of NF1 patients.
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author2 |
Yi-Ping Hsueh |
author_facet |
Yi-Ping Hsueh Yi-Ling Lin 林怡伶 |
author |
Yi-Ling Lin 林怡伶 |
spellingShingle |
Yi-Ling Lin 林怡伶 The roles of neurofibromin in neuronal morphogenesis |
author_sort |
Yi-Ling Lin |
title |
The roles of neurofibromin in neuronal morphogenesis |
title_short |
The roles of neurofibromin in neuronal morphogenesis |
title_full |
The roles of neurofibromin in neuronal morphogenesis |
title_fullStr |
The roles of neurofibromin in neuronal morphogenesis |
title_full_unstemmed |
The roles of neurofibromin in neuronal morphogenesis |
title_sort |
roles of neurofibromin in neuronal morphogenesis |
publishDate |
2008 |
url |
http://ndltd.ncl.edu.tw/handle/63383732737458127438 |
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