ALIX and ESCRT-III coordinately control cytokinetic abscission during germline stem cell division in vivo.

Åsmund H Eikenes,Knut Liestøl,Chloé B Steen,Harald Stenmark,Ioannis P Nezis,Kaisa Haglund,Juliette Mathieu,Anette Lie Christensen,Lene Malerød,Jean-René Huynh

doi:10.1371/journal.pgen.1004904

Abstract

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.

Highlights

Cytokinesis is the final step of cell division that leads to the physical separation of the two daughter cells
That the scaffold protein ALIX and the endosomal sorting complex required for transport (ESCRT)-III component Shrub are required for completion of abscission in Drosophila female germline stem cells
We find that ALIX and Shrub are required for completion of abscission in female germline stem cell (fGSC), that they co-localize during this process and that their direct interaction is required for abscission with normal kinetics

Summary

Introduction

Cytokinesis is the final step of cell division that leads to the physical separation of the two daughter cells. It is tightly controlled in space and time and proceeds in multiple steps via sequential specification of the cleavage plane, assembly and constriction of the actomyosin-based contractile ring (CR), formation of a thin intercellular bridge and abscission that separates the two daughter cells [1,2,3,4,5,6,7,8]. The mechanisms of the final abscission step of cytokinesis are less understood, especially in vivo in the context of different cell types in a multi-cellular organism [2, 4, 5]. In C. elegans embryos the MR plays an important role in scaffolding the abscission machinery even in the absence of MB MTs [20]

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Conclusion