Beyond gap junctions: Connexin43 and bone cell signaling.

Beyond gap junctions: Connexin43 and bone cell signaling.
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DOI:
10.1016/j.bone.2012.09.030
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发表时间:
2013-01
期刊:
影响因子:
4.1
通讯作者:
Bellido, Teresita
Bellido, Teresita
中科院分区:
医学2区
文献类型:
--
作者:
Plotkin, Lilian I.;Bellido, Teresita

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连接蛋白43(Cx43)是骨细胞中表达最丰富的间隙连接蛋白,在骨骼的细胞间通讯中起着重要作用。过去十年的发现揭示了Cx43半通道的功能,其表达在无对抗的浆细胞膜上,作为骨细胞与其细胞外环境之间的通信的介质。此外,通过其胞质C-末端结构域,Cx43作为支架蛋白,与结构和信号传导分子相关,导致细胞内信号传导的调节,而不依赖于通道活性。这种观点讨论的证据表明,通过这些不同的机制Cx43是一个关键组成部分的细胞内机制负责在骨中的信号转导响应药理学,激素和机械刺激。这一进展的知识的作用,连接蛋白增加了我们的理解的病理生理机制,调节骨细胞的功能,并提供了新的机会,治疗骨疾病。
Connexin 43 (Cx43) is the most abundant gap junction protein expressed in bone cells and plays a central role in cell-to-cell communication in the skeleton. Findings of the last decade uncovered functions of Cx43 hemichannels expressed on unopposed plasma cell membranes as mediators of the communication between bone cells and their extracellular milieu. Additionally, through its cytoplastmic C-terminus domain, Cx43 serves as a scaffolding protein that associates with structural and signaling molecules leading to regulation of intracellular signaling, independently of channel activity. This perspective discusses the evidence demonstrating that via these diverse mechanisms Cx43 is a key component of the intracellular machinery responsible for signal transduction in bone in response to pharmacologic, hormonal and mechanical stimuli. This advance in the knowledge of the role of connexins increases our understanding of the pathophysiological mechanisms that regulate bone cell function and provides new opportunities to treat bone diseases.
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