title: Centralspindlin in Rappaport's cleavage signaling.
abstract: Cleavage furrow in animal cell cytokinesis is formed by cortical constriction driven by contraction of an actomyosin network activated by Rho GTPase. Although the role of the mitotic apparatus in furrow induction has been well established, there remain discussions about the detailed molecular mechanisms of the cleavage signaling. While experiments in large echinoderm embryos highlighted the role of astral microtubules, data in smaller cells indicate the role of central spindle. Centralspindlin is a constitutive heterotetramer of MKLP1 kinesin and the non-motor CYK4 subunit and plays crucial roles in formation of the central spindle and recruitment of the downstream cytokinesis factors including ECT2, the major activator of Rho during cytokinesis, to the site of division. Recent reports have revealed a role of this centralspindlin-ECT2 pathway in furrow induction both by the central spindle and by the astral microtubules. Here, a unified view of the stimulation of cortical contractility by this pathway is discussed. Cytokinesis, the division of the whole cytoplasm, is an essential process for cell proliferation and embryonic development. In animal cells, cytokinesis is executed using a contractile network of actin filaments driven by a myosin-II motor that constricts the cell cortex (cleavage furrow ingression) into a narrow channel between the two daughter cells, which is resolved by scission (abscission) [1-3]. The anaphase-specific organization of the mitotic apparatus (MA, spindle with chromosomes plus asters) positions the cleavage furrow and plays a major role in spatial coupling between mitosis and cytokinesis [4-6]. The nucleus and chromosomes are dispensable for furrow specification [7-10], although they contribute to persistent furrowing and robust completion in some cell types [11,12]. Likewise, centrosomes are not essential for cytokinesis, but they contribute to the general fidelity of cell division [10,13-15]. Here, classical models of cleavage furrow induction are outlined, and a unified view of the stimulation of cortical contractility by the centralspindlin-ECT2 pathway is discussed.
authors.affiliation: Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Gibbet Hill Road CV4 7AL, United Kingdom. Electronic address: m.mishima@warwick.ac.uk.
authors.forename: Masanori
authors.initials: M
authors.lastname: Mishima
mesh_terms: D000818:Animals; D048749:Cytokinesis; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D060066:Protein Interaction Maps; D015398:Signal Transduction
chemical_list: D016547:Kinesins
keywords: Astral microtubules; Central spindle; Centralspindlin; Cleavage furrow; Cytokinesis; ECT2; Rappaport’s torus experiment; Rho