Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
Section on Membrane Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
J Cell Biol. 2019 May 6;218(5):1436-1451. doi: 10.1083/jcb.201901017. Epub 2019 Apr 1.
Cell-cell fusion remains the least understood type of membrane fusion process. However, the last few years have brought about major advances in understanding fusion between gametes, myoblasts, macrophages, trophoblasts, epithelial, cancer, and other cells in normal development and in diseases. While different cell fusion processes appear to proceed via similar membrane rearrangements, proteins that have been identified as necessary and sufficient for cell fusion (fusogens) use diverse mechanisms. Some fusions are controlled by a single fusogen; other fusions depend on several proteins that either work together throughout the fusion pathway or drive distinct stages. Furthermore, some fusions require fusogens to be present on both fusing membranes, and in other fusions, fusogens have to be on only one of the membranes. Remarkably, some of the proteins that fuse cells also sculpt single cells, repair neurons, promote scission of endocytic vesicles, and seal phagosomes. In this review, we discuss the properties and diversity of the known proteins mediating cell-cell fusion and highlight their different working mechanisms in various contexts.
细胞融合仍然是膜融合过程中了解最少的类型。然而,在过去的几年里,人们对配子、成肌细胞、巨噬细胞、滋养层、上皮细胞、癌细胞和其他正常发育和疾病细胞之间的融合有了重大的认识进展。虽然不同的细胞融合过程似乎通过类似的膜重排进行,但已被确定为细胞融合所必需和充分的蛋白质(融合蛋白)使用不同的机制。有些融合由单个融合蛋白控制;其他融合依赖于几种蛋白质,这些蛋白质要么在整个融合途径中协同作用,要么驱动不同的阶段。此外,一些融合要求融合蛋白存在于融合的两个膜上,而在其他融合中,融合蛋白只需要存在于一个膜上。值得注意的是,一些融合细胞的蛋白质还能塑造单个细胞、修复神经元、促进内吞小泡的分裂和封闭吞噬体。在这篇综述中,我们讨论了已知介导细胞-细胞融合的蛋白质的特性和多样性,并强调了它们在不同环境下的不同工作机制。