Eikenes Åsmund H, Malerød Lene, Christensen Anette Lie, Steen Chloé B, Mathieu Juliette, Nezis Ioannis P, Liestøl Knut, Huynh Jean-René, Stenmark Harald, Haglund Kaisa
Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Department of Genetics and Developmental Biology, Institut Curie, Paris, France; CNRS UMR3215, Inserm U934 F-75248, Paris, France.
PLoS Genet. 2015 Jan 30;11(1):e1004904. doi: 10.1371/journal.pgen.1004904. eCollection 2015 Jan.
Abscission is the final step of cytokinesis that involves the cleavage of the intercellular bridge connecting the two daughter cells. Recent studies have given novel insight into the spatiotemporal regulation and molecular mechanisms controlling abscission in cultured yeast and human cells. The mechanisms of abscission in living metazoan tissues are however not well understood. Here we show that ALIX and the ESCRT-III component Shrub are required for completion of abscission during Drosophila female germline stem cell (fGSC) division. Loss of ALIX or Shrub function in fGSCs leads to delayed abscission and the consequent formation of stem cysts in which chains of daughter cells remain interconnected to the fGSC via midbody rings and fusome. We demonstrate that ALIX and Shrub interact and that they co-localize at midbody rings and midbodies during cytokinetic abscission in fGSCs. Mechanistically, we show that the direct interaction between ALIX and Shrub is required to ensure cytokinesis completion with normal kinetics in fGSCs. We conclude that ALIX and ESCRT-III coordinately control abscission in Drosophila fGSCs and that their complex formation is required for accurate abscission timing in GSCs in vivo.
细胞脱离是胞质分裂的最后一步，涉及连接两个子细胞的细胞间桥的分裂。最近的研究对培养的酵母和人类细胞中控制细胞脱离的时空调节和分子机制有了新的见解。然而，后生动物活组织中的细胞脱离机制尚不清楚。在这里，我们表明，在果蝇雌性生殖系干细胞（fGSC）分裂过程中，ALIX和ESCRT-III组分Shrub是完成细胞脱离所必需的。fGSCs中ALIX或Shrub功能的丧失会导致细胞脱离延迟，并因此形成干细胞囊肿，其中子细胞链通过中体环和纺锤体与fGSC保持相互连接。我们证明ALIX和Shrub相互作用，并且在fGSCs的细胞动力学脱离过程中它们共定位于中体环和中体。从机制上讲，我们表明ALIX和Shrub之间的直接相互作用是确保fGSCs中细胞分裂以正常动力学完成所必需的。我们得出结论，ALIX和ESCRT-III协同控制果蝇fGSCs中的细胞脱离，并且它们的复合物形成对于体内GSCs中准确的细胞脱离时间是必需的。
