Breaking up is hard to do - membrane traffic in cytokinesis

Abstract

Throughout normal development, and in aberrant conditions such as cancer, cells divide by a process called cytokinesis. Most textbooks suggest that animal cells execute cytokinesis using an actomyosin-containing contractile ring, whereas plant cells generate a new cell wall by the assembly of a novel membrane compartment using vesicle-trafficking machinery in an apparently distinct manner. Recent studies have shown that cytokinesis in animal and plant cells may not be as distinct as these models imply - both have an absolute requirement for vesicle traffic. Moreover, some of the key molecular components of cytokinesis have been identified, many of which are proteins that function to control membrane traffic. Here, we review recent advances in this area.

Fig. 1

Model for membrane traffic during cytokinesis (A) MKLP1 and MgcRacGAP act to recruit the Rho guanine nucleotide-exchange factor (RhoGEF) ECT2 and activate RhoA (not shown), thereby driving contractile-ring formation and contraction (Piekny et al., 2005). The furrow then ingresses, leaving a thin intercellular connection between the cells, and a midbody-ring structure is assembled. (B) During furrowing, the composition of the plasma membrane (PM) of the furrow changes – levels of cholesterol, GM1 and PtdIns(4,5)P₂ increase (Desautels et al., 2001; Emoto et al., 2005; Field et al., 2005), PE redistributes into the outer leaflet (Emoto and Umeda, 2000). Increased levels of PtdIns(4,5)P₂ might be controlled by Rab35 (see text). The arrival of centriolin at the midbody ring is controlled by MKLP1 (Gromley et al., 2005). (C) Centriolin then recruits SNAPIN and exocyst components to the midbody ring (Gromley et al., 2005). (D) Recycling endosomes at the centrosome bud vesicles that contain Rab11-GTP (and which interact with FIP3 and Arf6) and traffic into the midbody (Wilson et al., 2005), presumably along microtubules using an unidentified motor protein. Secretory vesicles (probably derived from the TGN) also traffic into the midbody. These vesicles might contain VAMP8 and other cargo that is required for abscission. Rab35-positive vesicles also traffic into the furrow, perhaps to establish differential lipid domains that are enriched in PtdIns(4,5)P₂ (Kouranti et al., 2006). Bold arrows indicate traffic into the furrow. (E) Endosomal (Rab35-positive and/or Rab11-positive) and secretory vesicles accumulate in the midbody through the interaction with multiple proteins (e.g. FIP3 with Arf6, Rab11 or Cyk4, or Rab11 with exocyst components) (Fielding et al., 2005). The ESCRT complex might also function here to retrieve cargo from vesicles (Carlton and Martin-Serrano, 2007; Morita et al., 2007). Note that ER tubules are often observed within midbodies and might function to control signalling molecules such as Ca²⁺. (F) A signal for compound fusion might result in these vesicles fusing with the PM and themselves, resulting in abscission. This might include a direct role for the ESCRT machinery in resolving the thin cytoplasmic bridge. This compound fusion is possibly mediated by syntaxin 2 and VAMP8 (Low et al., 2003).