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首页> 外文学位 >Selectivity of connexin43 and connexin40 comprised gap junctions.
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Selectivity of connexin43 and connexin40 comprised gap junctions.

机译：连接蛋白43和连接蛋白40的选择性包括间隙连接。

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摘要

Gap junctions are aggregates of intercellular channels each formed of protein subunits termed connexins (Cx). Recently published data show that junctional dye permeability relative to conductance (permselectivity) varies across several orders of magnitude for Cx43 junctions, suggesting variable selectivity of the comprising Cx43 channels. Logical candidates for this variable selectivity are variability in charge or size selectivity. Consequently, junctional charge and size selectivities were determined in the current study by simultaneous measurement of junctional permeance to dyes of differing size or charge.;The results show that for a number of dyes differing in size, charge, chemical composition, and structure the primary determinant for selectivity through Cx43 gap junctions was the size of the dye permeant with this selectivity showing essentially no variability beyond that seen between incompletely divided cells, presumably representing the variability inherent to the measurement. As such, selectivity of dye-permeable Cx43 channels is well described by the physical dimensions of the channel pore acting essentially as a simple molecular sieve. The seemingly disparate dye selectivity and permselectivity results can be reconciled by the variable presence of a dye-impermeable but electrically conductive channel conformation for Cx43 channels, affording a possible mechanism for independent regulation of diffusion of larger molecules versus electrical conductance to smaller ions.;Cx40 junctions, known to be cation selective, also showed minimal variability in charge selectivity indicating that Cx40 charge selectivity is also an essentially fixed parameter. Co-expression of Cx40 and Cx43 lead to charge selectivities ranging from Cx43 to Cx40 with an average intermediate between the two. Activation of PKC leads to an increase in cationic selectivity of Cx40/Cx43 composed junctions by specifically reducing permeability through non-selective Cx43 channels favoring permeation through cation-selective Cx40 channels, allowing for junctional charge selectivity regulation.;The combined data suggest that selectivity properties for dye permeable channels composed of Cx43 or Cx40 are essentially fixed parameters of the channel pore. Only upon co-expression of these connexins is significant variability in selectivity seen. The differential effects of PKC-mediated phosphorylation on permeability of Cx43 and Cx40 channels then allows for regulation of junctional charge selectivity but only in cells expressing both connexins.
机译：间隙连接是细胞间通道的聚集体，每个通道间通道由称为连接蛋白（Cx）的蛋白质亚基形成。最近发布的数据显示，Cx43接头的染料相对于电导率的渗透率（渗透性）在几个数量级上变化，表明组成的Cx43通道具有不同的选择性。该可变选择性的逻辑候选者是电荷的可变性或尺寸选择性。因此，在本研究中，通过同时测量不同大小或电荷的染料的结合渗透率，确定了连接电荷和尺寸的选择性。结果表明，对于许多大小，电荷，化学组成和结构不同的染料，通过Cx43缝隙连接的选择性的决定因素是染料渗透物的大小，该选择性基本上没有变化，除了在不完全分裂的细胞之间看到的变化之外，这大概代表了测量固有的变化性。这样，可渗透染料的Cx43通道的选择性很好地通过基本上充当简单分子筛的通道孔的物理尺寸来描述。 Cx43通道的不渗透染料但具有导电性的通道构象的可变存在，可以使看似截然不同的染料选择性和渗透选择性结果相一致，从而为独立控制较大分子的扩散与较小离子的电导率提供了可能的机制。已知具有阳离子选择性的碳纳米管连接也显示出最小的电荷选择性变化，表明Cx40电荷选择性也是一个基本固定的参数。 Cx40和Cx43的共表达会导致电荷选择性介于Cx43至Cx40之间，且两者之间的平均中间值是。 PKC的活化通过特别降低非选择性Cx43通道的渗透性，有利于阳离子选择性Cx40通道的渗透，从而允许对结合电荷的选择性进行调节，从而导致Cx40 / Cx43组成的连接的阳离子选择性增加。对于由Cx43或Cx40组成的染料可渗透通道，基本上是通道孔的固定参数。仅在这些连接蛋白的共表达时，才能看到选择性的显着变化。 PKC介导的磷酸化对Cx43和Cx40通道的通透性的不同影响因此可以调节连接电荷的选择性，但只能在表达两种连接蛋白的细胞中进行。

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  • 作者

    Heyman, Nathanael.;

  • 作者单位

    The University of Arizona.;

  • 授予单位 The University of Arizona.;
  • 学科 Biology Physiology.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 132 p.
  • 总页数 132
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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