Physiological function of voltage-dependent Na^+ channel β-subunit as an adhesion molecule

电压依赖性Na^+通道β亚基作为粘附分子的生理功能

基本信息

项目摘要

Voltage-dependent Na^+ channel β-subunits contain a single extracellular Ig-like domain with structural similarity to the cell adhesion molecules. In this project, we have studied the regulatory mechanisms of expression and intracellular trafficking of the β-subunits as well as their role in cell differentiation.In cultured bovine adrenal chromaffin cells, insulin and IGF-1 increased cell surface expression of Na^+ channels. Insulin and IGF-1 increased Na^+ channel α-subunit mRNA level but not (β-subunit mRNA level. In rat pheochromocytoma PC 12 cells, neuronal differentiation by nerve growth factor increased β_1-subunit mRNA level but not β_3-subunit mRNA level, indicating that the mechanisms regulating the expression of a-subunit and β-subunits are different.When HEK293 cells were transfected with GFP tagged β-subunit constructs, β_1-Subunit-GFP was expressed strongly at the cell surface and weakly in endoplasmic reticulum. β_2-Subunit-GFP was expressed predominantly at cell surface, and these cells extended many microvilli. β_3-Subunit-GFP was expressed strongly at cell membrane and at intracellular spherical membrane structure, and these cells also extended microvilli, indicating that the intracellular trafficking and the physiological function of the β-subunits are different. In addition, PC12 cells expressing each subunit tagged with GFP extended neuritis even in the absence of nerve growth factor, and the effects of β_2-GFP or β_3-GFP were stronger than that of β_1-GFP. The neurite extending effects of nerve growth factor were more pronounced in each β-subunit-GFP expressing cells than in the control cells.These results indicate that β-subunits play a role in the regulation of cell differentiation, and that the intracellular trafficking mechanisms of the β-subunits and their regulatory mechanisms of expression are different.
电压依赖性 Na^+ 通道 β 亚基包含单个细胞外 Ig 样结构域,其结构与细胞粘附分子相似。在本项目中,我们研究了β亚基的表达和细胞内运输的调控机制及其在细胞分化中的作用。在培养的牛肾上腺嗜铬细胞中,胰岛素和IGF-1增加了细胞表面Na^+通道的表达。胰岛素和IGF-1增加Na^+通道α亚基mRNA水平,但不增加β亚基mRNA水平。在大鼠嗜铬细胞瘤PC 12细胞中,神经生长因子向神经元分化增加β_1-亚基mRNA水平,但不增加β_3-亚基mRNA水平,表明调节a-亚基和β-亚基表达的机制不同。 HEK293细胞用GFP标记的β亚基构建体转染,β_1-亚基-GFP在细胞表面强表达,在内质网中弱表达。 β_2-亚基-GFP主要在细胞表面表达,这些细胞延伸出许多微绒毛。 β_3-亚基-GFP 在细胞膜和 细胞内呈球形膜结构,并且这些细胞还延伸出微绒毛,表明β亚基的细胞内运输和生理功能是不同的。此外,即使在没有神经生长因子的情况下,表达GFP标记的各亚基的PC12细胞也能产生延伸性神经炎,且β_2-GFP或β_3-GFP的作用强于β_2-GFP或β_3-GFP。 β_1-GFP。神经生长因子的神经突延伸作用在各β亚基-GFP表达细胞中均比对照细胞更明显。这些结果表明β亚基在细胞分化的调节中发挥作用,并且β亚基的细胞内运输机制及其表达调节机制是不同的。

项目成果

期刊论文数量(38)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Yanagita T. et al.: "Destabilization of sodium channel α-subunit mRNA by constitutive phosphrylation of ERK : Negatively regulation of steady-state level of cell surface functional sodium channels"Molecular Pharmacol.ogy. 63. 1125-1136 (2003)
Yanagita T.等人:“通过ERK的组成型磷酸化使钠通道α-亚基mRNA不稳定:细胞表面钠功能通道的稳态水平的负调节”《分子药理学》63. 1125-1136 (2003)。
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    0
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Regulation of cell surface expression of voltage-dependent Nav1.7 sodium channels:: MRNA stability and posttranscriptional control in adrenal chromaffin cells
  • DOI:
    10.2741/1314
  • 发表时间:
    2004-05-01
  • 期刊:
  • 影响因子:
    3.1
  • 作者:
    Wada, A;Yanagita, T;Kobayashi, H
  • 通讯作者:
    Kobayashi, H
Molecular mechanisms and drug development in aquaporin water channel diseases : Aquaporin in the brain
水通道蛋白水通道疾病的分子机制和药物开发:大脑中的水通道蛋白
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    横尾 宏毅 他;Yokoo H. et al.;Wada A.et al.;Kobayashi H. et al.;Yanagita T. et al.;Kobayashi H. et al.;Kobayashi H. et al.
  • 通讯作者:
    Kobayashi H. et al.
Cell Biology of the Chromaffin Cells
嗜铬细胞的细胞生物学
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    横尾 宏毅 他;Yokoo H. et al.;Wada A.et al.;Kobayashi H. et al.;Yanagita T. et al.;Kobayashi H. et al.;Kobayashi H. et al.;Shiraishi S. et al.;Yokoo H. et al.;Yanagita T. et al.;Kobayashi H. et al.;Yanagita T. et al.
  • 通讯作者:
    Yanagita T. et al.
Pathophysiological function of adrenomedullin and proadrenomedullin N-terminal peptides in adrenal chromaffin cells.
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KOBAYASHI Hideyuki其他文献

KOBAYASHI Hideyuki的其他文献

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{{ truncateString('KOBAYASHI Hideyuki', 18)}}的其他基金

Elucidation of male infertility by epigenome analysis of iPS cells derived from male infertility and stem cell research
通过对源自男性不育症和干细胞研究的 iPS 细胞进行表观基因组分析来阐明男性不育症
  • 批准号:
    16K11072
  • 财政年份:
    2016
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The breakthrough of male infertily by stem cell research
干细胞研究突破男性不育症
  • 批准号:
    24791674
  • 财政年份:
    2012
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Educational Visual Acuity Assessment of Children with Profound and Multiple Disabilities
重度和多重残疾儿童的教育视力评估
  • 批准号:
    22531070
  • 财政年份:
    2010
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Research of the business dispute resolution process from a viewpointof legal negotiation
法律谈判视角下的商事纠纷解决流程研究
  • 批准号:
    22530076
  • 财政年份:
    2010
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification and analysis of human spermatogonial stem cells
人精原干细胞的鉴定与分析
  • 批准号:
    20791127
  • 财政年份:
    2008
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Regulatory mechanisms of expression and localization of aquaporin water channels in brain microvessels
脑微血管中水通道蛋白水通道表达和定位的调控机制
  • 批准号:
    17590473
  • 财政年份:
    2005
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Method of the Training and Instruction in the Use of Optical Aids for Partial Sighted
弱视配镜使用训练及指导方法
  • 批准号:
    16530625
  • 财政年份:
    2004
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Regulatory mechanism of aquaporin expression in cerebral microvessels : its pathophysiological significance
脑微血管水通道蛋白表达的调控机制及其病理生理意义
  • 批准号:
    13672394
  • 财政年份:
    2001
  • 资助金额:
    $ 2.43万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似国自然基金

工业用腈水合酶全新蛋白质翻译后调节体系self-subunit swapping的研究
  • 批准号:
    31070711
  • 批准年份:
    2010
  • 资助金额:
    35.0 万元
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Functional analysis of the voltage-dependent calcium channel β subunit in cardiac myocyte
心肌细胞电压依赖性钙通道β亚基的功能分析
  • 批准号:
    18590202
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甲状腺激素及其受体对促甲状腺激素α和β亚基基因的负调控
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电压依赖性钙通道β亚基的功能分析
  • 批准号:
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    2003
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Analysis of physiological function of calcium channel β subunit in heart muscle
心肌钙通道β亚基生理功能分析
  • 批准号:
    14370015
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    2002
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Involvement of the β-subunit in the potassium access channel of the sodium pump
β-亚基参与钠泵的钾通道
  • 批准号:
    10680623
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    1998
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血中 SP_1, hCG‐β subunit の測定による絨毛癌と破奇の鑑別
通过测定血液SP_1、hCG-β亚基来鉴别绒毛膜癌和异位
  • 批准号:
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    1983
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