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病毒限制因子 tetherin/BST2 将胞质分裂末期的残余物束缚在细胞表面。

The viral restriction factor tetherin/BST2 tethers cytokinetic midbody remnants to the cell surface.

机构信息

Membrane Traffic and Cell Division Lab, Institut Pasteur, UMR3691, CNRS, 25-28 rue du Dr Roux, 75015 Paris, France; Sorbonne Université, Collège Doctoral, 75005 Paris, France.

Membrane Traffic and Cell Division Lab, Institut Pasteur, UMR3691, CNRS, 25-28 rue du Dr Roux, 75015 Paris, France.

出版信息

Curr Biol. 2021 May 24;31(10):2203-2213.e5. doi: 10.1016/j.cub.2021.02.039. Epub 2021 Mar 11.

Abstract

The midbody at the center of the intercellular bridge connecting dividing cells recruits the machinery essential for the final steps of cytokinesis. Successive abscission on both sides of the midbody generates a free midbody remnant (MBR) that can be inherited and accumulated in many cancer, immortalized, and stem cells, both in culture and in vivo. Strikingly, this organelle was recently shown to contain information that induces cancer cell proliferation, influences cell polarity, and promotes dorso-ventral axis specification upon interaction with recipient cells. Yet the mechanisms by which the MBR is captured by either a daughter cell or a distant cell are poorly described. Here, we report that BST2/tetherin, a well-established restriction factor that blocks the release of numerous enveloped viruses from the surface of infected cells, plays an analogous role in retaining midbody remnants. We found that BST2 is enriched at the midbody during cytokinesis and localizes at the surface of MBRs in a variety of cells. Knocking out BST2 induces the detachment of MBRs from the cell surface, their accumulation in the extracellular medium, and their transfer to distant cells. Mechanistically, the localization of BST2 at the MBR membrane is both necessary and sufficient for the interaction between MBRs and the cell surface. We thus propose that BST2 tethers post-cytokinetic midbody remnants to the cell surface. This finding reveals new parallels between cytokinesis and viral biology that unexpectedly extend beyond the ESCRT-dependent abscission step.

摘要

位于连接分裂细胞的细胞间桥中心的中期体招募了对于胞质分裂最后步骤至关重要的机制。在中期体的两侧连续进行分离会产生一个游离的中期体残余物(MBR),它可以在许多癌症、永生化和干细胞中被继承和积累,无论是在培养中还是在体内。引人注目的是,最近有研究表明,这种细胞器含有诱导癌细胞增殖、影响细胞极性以及在与受体细胞相互作用时促进背腹轴特化的信息。然而,MBR 被子细胞或远离的细胞捕获的机制仍描述不清。在这里,我们报告说 BST2/ tetherin,一种阻止许多包膜病毒从受感染细胞表面释放的成熟限制因子,在保留中期体残余物方面发挥着类似的作用。我们发现 BST2 在胞质分裂过程中在中期体中富集,并在各种细胞中定位于 MBR 的表面。敲除 BST2 会诱导 MBR 从细胞膜上脱离,积累在细胞外介质中,并转移到远处的细胞中。从机制上讲,BST2 在 MBR 膜上的定位对于 MBR 与细胞膜之间的相互作用是必要和充分的。因此,我们提出 BST2 将胞质分裂后的中期体残余物系在细胞膜上。这一发现揭示了细胞分裂和病毒生物学之间新的相似性,这些相似性出乎意料地超出了 ESCRT 依赖性分离步骤。

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