Structural basis for the selective permeability of channels made of communicating junction proteins.

Structural basis for the selective permeability of channels made of communicating junction proteins.
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DOI:
10.1016/j.bbamem.2012.02.003
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发表时间:
2013-01
影响因子:
3.4
通讯作者:
Burt, Janis M.
Burt, Janis M.
中科院分区:
生物学3区
文献类型:
--
作者:
Ek-Vitorin, Jose F.;Burt, Janis M.

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间隙连接通道的开放状态从它们响应于施加的细胞间(跨连接/跨通道)电压梯度而被小离子渗透是明显的。开放通道允许可变量的电流在恒定的细胞间电压差的情况下从细胞到细胞传输,这表明通道开放/关闭可以是完全的或部分的。这种开放状态选择的生理意义可以说是连接调节的主要关注点。由于间隙连接对许多物质都是可渗透的,因此,研究每个开放状态是否以及如何影响分子的细胞间扩散是明智的,这些分子与载流离子一样有价值,但比载流离子更不易检测。据推测,被认为是通道电导率的变化的结构变化将显着改变其极限直径接近孔的极限直径的分子的transjunctional扩散。此外,在宏观或单通道水平上,对某些分子的连接渗透性可能发生变化,而电导率没有明显变化。开放的缝隙连接通道允许通过简单扩散在接触细胞之间交换细胞质渗透物。这些渗透物的身份,以及它们交界处交换的功能环境和后果,目前构成了该领域最紧迫(和要求)的主题。在这里,我们考虑调节这种交换的必要性,可能的机制(S)和结构元素可能参与这样的调节,以及如何调节现象可以被视为化学与电耦合的变化;我们的集体知识的交界处通信的整体反映,然后应用于建议新的研究途径。
The open state(s) of gap junction channels is evident from their permeation by small ions in response to an applied intercellular (transjunctional/transchannel) voltage gradient. That an open channel allows variable amounts of current to transit from cell-to-cell in the face of a constant intercellular voltage difference indicates channel open/closing can be complete or partial. The physiological significance of such open state options is, arguably, the main concern of junctional regulation. Because gap junctions are permeable to many substances, it is sensible to inquire whether and how each open state influences the intercellular diffusion of molecules as valuable as, but less readily detected than current-carrying ions. Presumably, structural changes perceived as shifts in channel conductivity would significantly alter the transjunctional diffusion of molecules whose limiting diameter approximates the pore’s limiting diameter. Moreover, changes in junctional permeability to some molecules might occur without evident changes in conductivity, either at macroscopic or single channel level. Open gap junction channels allow the exchange of cytoplasmic permeants between contacting cells by simple diffusion. The identity of such permeants, and the functional circumstances and consequences of their junctional exchange presently constitute the most urgent (and demanding) themes of the field. Here, we consider the necessity for regulating this exchange, the possible mechanism(s) and structural elements likely involved in such regulation, and how regulatory phenomena could be perceived as changes in chemical vs. electrical coupling; an overall reflection on our collective knowledge of junctional communication is then applied to suggest new avenues of research.
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