Mohler W A, Simske J S, Williams-Masson E M, Hardin J D, White J G
Laboratory of Molecular Biology, University of Wisconsin, Madison 53706, USA.
Curr Biol. 1998 Sep 24;8(19):1087-90. doi: 10.1016/s0960-9822(98)70447-6.
Cell fusions produce multinucleate syncytia that are crucial to the structure of essential tissues in many organisms [1-5]. In humans the entire musculature, much of the placenta, and key cells in bones and blood are derived from cell fusion. Yet the developmental fusion of cell membranes has never been directly observed and is poorly understood. Similarity between viral fusion proteins and recently discovered cellular proteins implies that both cell-cell and virus-cell fusion may occur by a similar mechanism [6-8]. Paradoxically, however, fusion of enveloped viruses with cells involves an opening originating as a single pore [9-11], whereas electron microscopy studies of cell-cell fusion describe simultaneous breakdown of large areas of membrane [12, 13]. Here, we have shown that developmental cell fusion is indeed consistent with initiation by a virus-like, pore-forming mechanism. We examined live cell fusions in the epithelia of Caenorhabditis elegans embryos by a new method that integrates multiphoton, confocal, and electron microscopy. The fusion aperture always originated at a single point restricted to the apical adherens junction and widened slowly as a radial wavefront. The fusing membranes dispersed by vesiculation, rather than simple unfolding of the conjoined double bilayer. Thus, in these cells fusion appears to require two specialized sequential processes: formation of a unique primary pore and expansion of the opening by radial internalization of the interacting cell membranes.
细胞融合产生多核的合体细胞，这对许多生物体中重要组织的结构至关重要[1 - 5]。在人类中，整个肌肉组织、大部分胎盘以及骨骼和血液中的关键细胞都源自细胞融合。然而，细胞膜的发育融合从未被直接观察到，人们对此也知之甚少。病毒融合蛋白与最近发现的细胞蛋白之间的相似性表明，细胞 - 细胞融合和病毒 - 细胞融合可能通过类似的机制发生[6 - 8]。然而，矛盾的是，包膜病毒与细胞的融合涉及从单个孔开始的开口形成[9 - 11]，而细胞 - 细胞融合的电子显微镜研究描述的是大片膜的同时破裂[12, 13]。在这里，我们已经表明，发育性细胞融合确实与一种类似病毒的成孔机制引发的过程一致。我们通过一种整合了多光子、共聚焦和电子显微镜的新方法，研究了秀丽隐杆线虫胚胎上皮中的活细胞融合。融合孔总是起源于一个局限于顶端黏着连接的单点，并作为一个径向波阵面缓慢扩大。融合的膜通过囊泡化分散，而不是通过连体双分子层的简单展开。因此，在这些细胞中，融合似乎需要两个专门的连续过程：形成一个独特的初级孔以及通过相互作用细胞膜的径向内化来扩大开口。
