Cell Division

A Platform for Signaling Cytokinesis

Science's STKE  13 Dec 2005:
Vol. 2005, Issue 314, pp. tw443
DOI: 10.1126/stke.3142005tw443

Ng et al. implicated cholesterol-, sphingolipid-, and signaling molecule-rich plasma membrane microdomains (thought to form signaling platforms involved in various cellular processes) in assembly of a signaling pathway critical to cytokinesis. During cytokinesis, the last stage of cell division, an actin-based ring at the equator constricts to split the cell in two. Ng et al. found that, whereas fluorescent cholera toxin subunit B (which detects ganglioside GM1--a marker for cholesterol-rich domains) distributed across the surface of live sea urchin eggs during interphase, it moved toward the site of the future cleavage furrow during anaphase, becoming concentrated in the deepening furrow. Wheat germ agglutinin showed a similar pattern of movement, and filipin staining of fixed eggs revealed a cholesterol-rich band around the cell equator. The band appeared coincidentally with the contractile ring and depended on F-actin as well as on microtubules (required for formation of the furrow) and myosin II light chain phosphorylation (required for actin ring assembly). Tyrosine-phosphorylated proteins accumulated in the cleavage furrow during cytokinesis, and isolated detergent-resistant membranes (believed to consist of cholesterol-rich membrane microdomains) contained GM1, Src family proteins, and the Src effector phospholipase C-γ (PLC-γ). Tyrosine phosphorylation of 55 kD Src and of PLC-γ was increased in dividing cells compared with those at interphase, and this was inhibited by depletion of cholesterol with filipin (which also blocked cytokinesis). Pharmacological analysis further implicated Src activity and PLC-γ in cleavage furrow progression and cytokinesis. Thus, the authors conclude that formation of a specialized membrane domain at the cell equator is critical for animal cell cytokinesis.

M. M. Ng, F. Chang, D. R. Burgess, Movement of membrane domains and requirement of membrane signaling molecules for cytokinesis. Dev. Cell 9, 781-790 (2005). [PubMed]