Manipulating connexin communication channels: use of peptidomimetics and the translational outputs.
Manipulating connexin communication channels: use of peptidomimetics and the translational outputs.
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DOI：
10.1007/s00232-012-9488-5
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发表时间：
2012-08
影响因子：
2.4
通讯作者：
Leybaert, Luc
中科院分区：
文献类型：
--
作者：
Evans, W. Howard;Bultynck, Geert;Leybaert, Luc
缝隙连接是多细胞生物的重要组成部分。它们提供细胞到细胞通道途径，使组织和器官中的直接细胞间通讯和细胞协调成为可能。通道由连接蛋白（Cx）膜蛋白家族构成。它们在细胞内寡聚化，产生由围绕中央通道排列的六个亚基组成的半通道（连接子）。在转移到质膜后，Cx半通道（CxHcs）阵列与相邻附着细胞中的伴侣相互作用并偶联以产生间隙连接。Cx通道已经使用一系列技术方法进行了研究。首先使用对应于Cxs的胞外和胞内区域中的序列的短肽来产生表位特异性抗体，这有助于研究间隙连接的组织和功能。随后，肽本身，特别是Gap26和Gap27，衍生自连接蛋白43（Cx43）（一种广泛分布的Cx）的两个细胞外环中的每一个的模拟肽，已被广泛应用于阻断Cx通道和探测细胞通讯的生物学。随后，在细胞内环中，特别是在Cx43的细胞内羧基尾部的末端，进一步开发了一系列短肽模拟序列。肽模拟物的主要抑制作用发生在位于细胞质膜未贴壁区域的CxHcs处，随后抑制跨间隙连接发生的细胞偶联。CxHcs通过增加其开放概率来响应一系列环境条件。肽模拟物提供了一种以一定选择性阻断CxHcs作用的方法。此外，它们越来越多地应用于解决被认为影响Cx通道操作的一系列环境应力的病理后果。Cx肽模拟物在开发新的治疗方法中显示出作为候选物的希望，用于抑制和逆转对CxHcs造成的损伤，特别是在心脏和脑功能中的缺氧和缺血中。
Gap junctions are key components underpinning multicellularity. They provide cell to cell channel pathways that enable direct intercellular communication and cellular coordination in tissues and organs. The channels are constructed of a family of connexin (Cx) membrane proteins. They oligomerize inside the cell, generating hemichannels (connexons) composed of six subunits arranged around a central channel. After transfer to the plasma membrane, arrays of Cx hemichannels (CxHcs) interact and couple with partners in neighboring attached cells to generate gap junctions. Cx channels have been studied using a range of technical approaches. Short peptides corresponding to sequences in the extra- and intracellular regions of Cxs were used first to generate epitope-specific antibodies that helped studies on the organization and functions of gap junctions. Subsequently, the peptides themselves, especially Gap26 and -27, mimetic peptides derived from each of the two extracellular loops of connexin43 (Cx43), a widely distributed Cx, have been extensively applied to block Cx channels and probe the biology of cell communication. The development of a further series of short peptides mimicking sequences in the intracellular loop, especially the extremity of the intracellular carboxyl tail of Cx43, followed. The primary inhibitory action of the peptidomimetics occurs at CxHcs located at unapposed regions of the cell’s plasma membrane, followed by inhibition of cell coupling occurring across gap junctions. CxHcs respond to a range of environmental conditions by increasing their open probability. Peptidomimetics provide a way to block the actions of CxHcs with some selectivity. Furthermore, they are increasingly applied to address the pathological consequences of a range of environmental stresses that are thought to influence Cx channel operation. Cx peptidomimetics show promise as candidates in developing new therapeutic approaches for containing and reversing damage inflicted on CxHcs, especially in hypoxia and ischemia in the heart and in brain functions.
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DOI：
10.1073/pnas.95.26.15735
发表时间：
1998-12-22
影响因子：
11.1
作者：
Cotrina, ML;Lin, JHC;Nedergaard, M
通讯作者：
Nedergaard, M
影响因子：
5
作者：
Clarke, Thomas C.;Williams, Oliver J. S.;Evans, W. Howard
通讯作者：
Evans, W. Howard
影响因子：
38.3
作者：
Bhabra, Gevdeep;Sood, Aman;Case, Charles Patrick
通讯作者：
Case, Charles Patrick
影响因子：
3.7
作者：
Clair, Caroline;Combettes, Laurent;Van Nlieu, Guy Tran
通讯作者：
Van Nlieu, Guy Tran
影响因子：
4
作者：
Boitano, S;Dirksen, ER;Evans, WH
通讯作者：
Evans, WH