The chromosomal passenger complex controls the function of endosomal sorting complex required for transport-III Snf7 proteins during cytokinesis

Luisa Capalbo,David M Glover,Pier Paolo D'Avino,Zuni I Bassi,Tetsuya Takeda,Emilie Montembault

doi:10.1098/rsob.120070

Abstract

SummaryCytokinesis controls the proper segregation of nuclear and cytoplasmic materials at the end of cell division. The chromosomal passenger complex (CPC) has been proposed to monitor the final separation of the two daughter cells at the end of cytokinesis in order to prevent cell abscission in the presence of DNA at the cleavage site, but the precise molecular basis for this is unclear. Recent studies indicate that abscission could be mediated by the assembly of filaments comprising components of the endosomal sorting complex required for transport-III (ESCRT-III). Here, we show that the CPC subunit Borealin interacts directly with the Snf7 components of ESCRT-III in both Drosophila and human cells. Moreover, we find that the CPC's catalytic subunit, Aurora B kinase, phosphorylates one of the three human Snf7 paralogues—CHMP4C—in its C-terminal tail, a region known to regulate its ability to form polymers and associate with membranes. Phosphorylation at these sites appears essential for CHMP4C function because their mutation leads to cytokinesis defects. We propose that CPC controls abscission timing through inhibition of ESCRT-III Snf7 polymerization and membrane association using two concurrent mechanisms: interaction of its Borealin component with Snf7 proteins and phosphorylation of CHMP4C by Aurora B.

Highlights

Cytokinesis, the final separation of two daughter cells at the end of cell division, requires the coordinated action of several proteins that promote the formation and ingression of a cleavage furrow that bisects the dividing cell
We propose that chromosomal passenger complex (CPC) controls abscission timing in both flies and human cells by regulating the function of endosomal sorting complexes required for transport (ESCRTs)-III Snf7 proteins during cytokinesis through the interaction of its Borealin component with the N-terminus of Shrb/CHMP4 proteins and Aurora B-mediated phosphorylation of the CHMP4C regulatory linker tail
In a proteomic survey of complexes involved in cell division in Drosophila, we tagged the CPC Borealin-related (Borr) component with two IgG-binding domains of Protein A (PtA) at either its N- or C-terminus

Summary

Introduction

Cytokinesis, the final separation of two daughter cells at the end of cell division, requires the coordinated action of several proteins that promote the formation and ingression of a cleavage furrow that bisects the dividing cell. Many key cytokinesis proteins localize to an array of anti-parallel and interdigitating microtubules known as the central spindle, which forms between the segregating anaphase chromosomes during furrow ingression [1]. The central spindle and its associated proteins control furrow formation and ingression, the transport of membrane vesicles to the cleavage site and the final abscission of the two daughter cells [2,3,4]. In the final stages of cytokinesis, the central spindle. License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited

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