Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch (UTMB), 105 11th Street, Galveston, TX 77555, USA.
Department of Surgery and TEAM Health Anesthesia, University of South Florida, 2 Tampa General Circle, Tampa, FL 33606, USA.
Int J Mol Sci. 2022 May 30;23(11):6133. doi: 10.3390/ijms23116133.
The history of direct cell-cell communication has evolved in several small steps. First discovered in the 1930s in invertebrate nervous systems, it was thought at first to be an exception to the "cell theory", restricted to invertebrates. Surprisingly, however, in the 1950s, electrical cell-cell communication was also reported in vertebrates. Once more, it was thought to be an exception restricted to excitable cells. In contrast, in the mid-1960s, two startling publications proved that virtually all cells freely exchange small neutral and charged molecules. Soon after, cell-cell communication by gap junction channels was reported. While gap junctions are the major means of cell-cell communication, in the early 1980s, evidence surfaced that some cells might also communicate via membrane pores. Questions were raised about the possible artifactual nature of the pores. However, early in this century, we learned that communication via membrane pores exists and plays a major role in medicine, as the structures involved, "tunneling nanotubes", can rescue diseased cells by directly transferring healthy mitochondria into compromised cells and tissues. On the other hand, pathogens/cancer could also use these communication systems to amplify pathogenesis. Here, we describe the evolution of the discovery of these new communication systems and the potential therapeutic impact on several uncurable diseases.
细胞间直接通讯的历史是在几个小步骤中发展起来的。它最初于 20 世纪 30 年代在无脊椎动物神经系统中被发现，起初被认为是“细胞学说”的一个例外，仅限于无脊椎动物。然而，令人惊讶的是，在 20 世纪 50 年代，电细胞间通讯也在脊椎动物中被报道。同样，它被认为是仅限于可兴奋细胞的例外。相比之下，在 20 世纪 60 年代中期，两篇引人注目的出版物证明，几乎所有细胞都可以自由交换小的中性和带电分子。不久之后，间隙连接通道的细胞间通讯被报道。虽然间隙连接是细胞间通讯的主要方式，但在 20 世纪 80 年代初，有证据表明一些细胞也可能通过膜孔进行通讯。有人对这些孔可能具有人为性质提出了质疑。然而，在本世纪初，我们了解到通过膜孔进行通讯的存在，并在医学中发挥了重要作用，因为所涉及的结构，“隧道纳米管”，可以通过直接将健康的线粒体转移到受损的细胞和组织中来拯救患病细胞。另一方面，病原体/癌症也可以利用这些通讯系统来放大发病机制。在这里，我们描述了这些新通讯系统的发现的演变以及它们对几种无法治愈的疾病的潜在治疗影响。
