Gap junctions between cells expressing connexin 43 or 32 show inverse permselectivity to adenosine and ATP
Gap junctions between cells expressing connexin 43 or 32 show inverse permselectivity to adenosine and ATP
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DOI：
10.1074/jbc.m109797200
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发表时间：
2002-09-27
影响因子：
4.8
通讯作者：
Lampe, PD
中科院分区：
文献类型：
--
作者：
Goldberg, GS;Moreno, AP;Lampe, PD
由连接蛋白家族的蛋白质组成的间隙连接是直接连接相邻细胞的细胞质，允许小亲水分子在细胞间转移的唯一通道。间隙连接通信对于动物和人类的正常发育和健康至关重要。虽然研究通过间隙连接的生物分子非常重要，但内源性跨连接代谢物的鉴定具有挑战性。为了帮助解决这个问题，我们开发了一种分层培养系统来识别和量化通过间隙连接在细胞之间传递的内源性分子的转移。利用这些技术，我们已经确定了几个内源性分子在Cx32和Cx43组成的通道之间表现出差异转移。例如，腺苷通过Cx32形成的通道的能力提高了约12倍。相比之下，AMP和ADP通过Cx43形成的通道的传递能力提高了约8倍，ATP的传递能力提高了300倍以上。因此，磷酸加入到腺苷中似乎将其相对渗透性从Cx32形成的通道转移到Cx43形成的通道。这表明功能上的影响，因为细胞的能量状态可以通过连接蛋白表达和通道形成来控制。
Gap junctions, composed of proteins from the connexin family, are the only channels that directly connect the cytoplasm of adjacent cells to allow for the intercellular transfer of small hydrophilic molecules. Gap junctional communication is essential for proper development and health in animals and humans. Whereas the study of biological molecules that pass through gap junctions is extremely important, the identification of endogenous transjunctional metabolites is challenging. To help address this problem, we have developed a layered culture system to identify and quantitate the transfer of endogenous molecules that pass between cells through gap junctions. Using these techniques, we have identified several endogenous molecules that showed differential transfer between channels composed of Cx32 versus Cx43. For example, adenosine passed about 12-fold better through channels formed by Cx32. In contrast, AMP and ADP passed about 8-fold better, and ATP greater than 300-fold better, through channels formed by Cx43. Thus, addition of phosphate to adenosine appears to shift its relative permeability from channels formed by Cx32 to channels formed by Cx43. This suggests functional consequence because the energy status of a cell could be controlled via connexin expression and channel formation.