The significance of phosphorylation of neurofilament protein
The significance of phosphorylation of neurofilament protein
批准号:
06680738
负责人:
GOTOW Takahiro
金额:
$1.22万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
1994
资助国家:
日本
项目状态:
已结题
起止时间:
1994 至 1996
中文摘要
在神经元中,神经细丝在胞体和树突中相对较少,但在轴突中含量较多。除了这种NF极性,NF亚单位蛋白,特别是NF-H,在轴突中高度磷酸化,而在体细胞和树突中磷酸化程度要低得多。核因子-H在核心丝之间形成交叉桥是必不可少的,我们认为它的磷酸化似乎是形成发育良好的交叉桥所必需的。为了证实我们的观点,在这三年中,我们在核因子-H磷酸化与核因子组织之间的关系方面取得了五个主要结果。1)在较粗的有髓轴突中,核心丝和交叉桥排列规则,核因子-H的磷酸化程度较高,而在较细的轴突中,核心丝和交叉桥的排列规则和磷酸化程度较低,微管明显。2)在兰维尔结节,轴突直径变小,核心丝距离更近,交叉桥不那么规则,NF-H的磷酸化程度低于t…更多的是同一轴突的剩余部分。3)向培养的非神经元或神经元样细胞显微注射NF-H蛋白后,NF-H被掺入中间丝中,当它被磷酸化时,往往会在交叉桥中形成频率较高的细丝束。4).体外实验表明,尽管我们正在研究哪种条件下的核因子-H的磷酸化对这种相互作用更有效,但体外实验表明,核因子可以通过核因子-H形成的交叉桥与微管或线粒体相互作用。5).目前,我们正在阐明髓鞘形成与中枢神经系统髓鞘生成受阻的Jimpy mutanat小鼠的髓鞘形成和NF-H组织或NF-H磷酸化之间的关系。刚刚发现,髓鞘缺陷轴突中非磷酸化形式的核因子-H急剧增加,核心细丝比对照组更致密。综上所述,我们的研究结果表明,神经营养因子-H的磷酸化与神经营养因子的组织化之间存在着密切的关系,并且轴突通过神经营养因子-H的磷酸化而在交叉桥和核心纤维中有规则的排列是必要的。此外,还认为髓鞘形成增加了核因子-H的磷酸化水平,从而导致轴突中正常的核因子有机化。较少
英文摘要
In neurons, neurofilaments (NF) are relatively fewer in somata and dendrites but abundant in axons. In addition to this NFpolarity, the NF subunit protein, especially NF-H,is extremely phosphorylated in axons, and much less phosphorylated in somata and dendrites. NF-H is essential for forming crossbridges between core filaments, and we are thinking that its phosphorylation seems necessary to form well-developed crossbridges. To confirm our idea, we have obtained five main results on the relationship between NF-H phosphorylation and NF organization during these three years. 1).Both core filaments and crossbridges were regular in arrangement and NF-H was well phosphorylated in thicker myelinated axons, whereas they were less regular and less phosphorylated in thinner axons where microtubules were conspicuous. 2).In the node of Ranvier, where axon becomes smaller in diameter, core filametns were closer to each other and crossbridges were less regular and NF-H wa less phosphorylated than t … More he remainder of the same axon. 3).After microinjection of NF-H protein into cultured nonneuronal or neuron-like cells, NF-H was incorported into intermediate filaments and tended to make bundles of the filaments with rather higher frequency in crossbridges when it was phosphorylated. 4).In vitro experiments showed that NF could interact with microtubules or mitochondria through the crossbridges formed by NF-H,although we are now examining which condition in phosphorylation of NF-H is more efficient for such interactions. 5).At present, we are clarifying the relationship between the myelination and NF organization or NF-H phosphorylation with jimpy mutanat mice, where the myelinogenesis is distrupted in the central nervous system. It has just been found that nonphosphorylated form of NF-H increases drastically and core filaments are much more compact in the myelin-deficient axons than in controls. In conclusion, our data indicate that there is an intimate relationship between NF-H phosphorylation and NF organization, and also that it is necessary for the axon to have regular arrangements in crossbridges and finally in core filaments by NF-H phosphorylation. Furthermore, it is considered that the myelination increases in NF-H phosphorylation level resulting in normal NF oganization in axons. Less
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Gotow, T., Sakata, M., Funakoshi, T.and Uchiyama, Y.: "Preferential localization of annexin V to the axon terminal" Neuroscience. 75. 507-521 (1996)
Gotow, T.、Sakata, M.、Funakoshi, T. 和 Uchiyama, Y.:“膜联蛋白 V 优先定位于轴突末端”神经科学。
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Takeda,M et al.: "Neurofilament pathology in neurodegenerative process of Alzheimer disease" Ann,Psychiat.5. 113-126 (1995)
Takeda,M 等人:“阿尔茨海默病神经退行性过程中的神经丝病理学”Ann,Psychiat.5。
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Gotow, T.: "Dynamic structure and function of neurofilaments" Annals of Psychiatry. 5. 91-111 (1995)
Gotow, T.:“神经丝的动态结构和功能”精神病学年鉴。
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Gotow,T.,Tanaka,T.,Nakamura,Y.,Takeda M.: "Dephosphorylation of the largest neurofilament subumit protein influences the structure of crossbridges in reassembled neurofilaments" Journal of Cell Science. 107. 1949-1957 (1994)
Gotow,T.、Tanaka,T.、Nakamura,Y.、Takeda M.:“最大的神经丝亚基蛋白的去磷酸化影响重新组装的神经丝中的横桥结构”《细胞科学杂志》。
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Gotow, T.: "The organization of neurofilaments accumulated in perikaryon following aluminum infoxication : relationship between structure and phosphorylation of neurofilaments" Neuroscience. 64. 553-569 (1995)
Gotow, T.:“铝中毒后在核周积累的神经丝的组织:神经丝的结构和磷酸化之间的关系”神经科学。
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共 21 条
Influences of phytochemicals on age- and disease-related degenerative neurons
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批准号:21590225
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$3.08万
-
财政年份:2009
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负责人:GOTOW Takahiro
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依托单位:
Axonal degenerations with aging and their rescue by genetic and nutritional manipulations
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批准号:16590158
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.05万
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财政年份:2004
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负责人:GOTOW Takahiro
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依托单位:
Cytoskeletons and cell death-associated proteins expressed in neuronal cells in the neurofilament gene-manipulated mice
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批准号:14570030
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.24万
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财政年份:2002
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负责人:GOTOW Takahiro
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依托单位:
Relationship between neurodegenerative diseases and neurofilaments accumulated in somata and/or axons
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批准号:12680741
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.37万
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财政年份:2000
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负责人:GOTOW Takahiro
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依托单位:
The role of neurofilament and mitochondria in the neuronal cell death
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批准号:10670016
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$1.98万
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财政年份:1998
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负责人:GOTOW Takahiro
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依托单位:
Molecular anatomical analysis of neurofilament
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批准号:03807001
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项目类别:Grant-in-Aid for General Scientific Research (C)
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资助金额:$0.83万
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财政年份:1991
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负责人:GOTOW Takahiro
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依托单位:
海外基金