Levin Michael
Forsyth Center for Regenerative and Devlopmental Biology, Forsyth Institute, and Developmental Biology Department, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Prog Biophys Mol Biol. 2007 May-Jun;94(1-2):186-206. doi: 10.1016/j.pbiomolbio.2007.03.005. Epub 2007 Mar 16.
Gap junctions permit the direct passage of small molecules from the cytosol of one cell to that of its neighbor, and thus form a system of cell-cell communication that exists alongside familiar secretion/receptor signaling. Because of the rich potential for regulation of junctional conductance, and directional and molecular gating (specificity), gap junctional communication (GJC) plays a crucial role in many aspects of normal tissue physiology. However, the most exciting role for GJC is in the regulation of information flow that takes place during embryonic development, regeneration, and tumor progression. The molecular mechanisms by which GJC establishes local and long-range instructive morphogenetic cues are just beginning to be understood. This review summarizes the current knowledge of the involvement of GJC in the patterning of both vertebrate and invertebrate systems and discusses in detail several morphogenetic systems in which the properties of this signaling have been molecularly characterized. One model consistent with existing data in the fields of vertebrate left-right patterning and anterior-posterior polarity in flatworm regeneration postulates electrophoretically guided movement of small molecule morphogens through long-range GJC paths. The discovery of mechanisms controlling embryonic and regenerative GJC-mediated signaling, and identification of the downstream targets of GJC-permeable molecules, represent exciting next areas of research in this fascinating field.
间隙连接允许小分子从一个细胞的胞质溶胶直接进入其相邻细胞的胞质溶胶,从而形成一个细胞间通讯系统,该系统与常见的分泌/受体信号传导并存。由于间隙连接电导的调节潜力巨大,以及具有方向性和分子门控(特异性),间隙连接通讯(GJC)在正常组织生理学的许多方面都发挥着关键作用。然而,GJC最令人兴奋的作用在于调节胚胎发育、再生和肿瘤进展过程中发生的信息流。GJC建立局部和远程指导性形态发生线索的分子机制才刚刚开始被理解。这篇综述总结了目前关于GJC参与脊椎动物和无脊椎动物系统模式形成的知识,并详细讨论了几个已对该信号传导特性进行分子表征的形态发生系统。一个与脊椎动物左右模式形成和平扁虫再生前后极性领域现有数据一致的模型假设,小分子形态发生素通过远程GJC路径进行电泳引导运动。控制胚胎和再生GJC介导信号传导的机制的发现,以及GJC可渗透分子下游靶点的鉴定,代表了这个迷人领域中令人兴奋的下一个研究方向。