ESCRT function in cytokinesis: location, dynamics and regulation by mitotic kinases

Abstract

Mammalian cytokinesis proceeds by constriction of an actomyosin ring and furrow ingression, resulting in the formation of the midbody bridge connecting two daughter cells. At the centre of the midbody resides the Flemming body, a dense proteinaceous ring surrounding the interlocking ends of anti-parallel microtubule arrays. Abscission, the terminal step of cytokinesis, occurs near the Flemming body. A series of broad processes govern abscission: the initiation and stabilisation of the abscission zone, followed by microtubule severing and membrane scission-The latter mediated by the endosomal sorting complex required for transport (ESCRT) proteins. A key goal of cell and developmental biologists is to develop a clear understanding of the mechanisms that underpin abscission, and how the spatiotemporal coordination of these events with previous stages in cell division is accomplished. This article will focus on the function and dynamics of the ESCRT proteins in abscission and will review recent work, which has begun to explore how these complex protein assemblies are regulated by the cell cycle machinery.

Figure 1

Schematic model for abscission in mammalian cells. In panel (A), CEP55 (Centrosomal protein of 55 kDa) has first recruited ESCRT-I components (Tumour susceptibility gene 101 (TSG101), apoptosis-linked gene 2-interacting protein (ALIX)) to the Flemming body, followed by the recruitment of ESCRT-III; (B) The Recruitment of the ATPase VPS4 to this assembly is proposed to mediate breakage or remodeling of the ESCRT-III, facilitating the appearance of ESCRT-III at the abscission zone (for details of different models for this event, see text); (C) Constriction at the secondary ingression site may be driven either by fusion of endosomal vesicles with the plasma membrane (inset), or by ESCRT-III interactions with the plasma membrane (see text). The possible role of lipid domains and the Rho GTPase activating protein (RhoGAP) (insert) is discussed in the text; and (D) Scission is thought to be driven by the ESCRT-III/VPS4 complex.