title: Targeting of the RhoGEF Ect2 to the equatorial membrane controls cleavage furrow formation during cytokinesis.
abstract: In animal cells, formation of the cytokinetic furrow requires activation of the GTPase RhoA by the guanine nucleotide exchange factor Ect2. How Ect2, which is associated with the spindle midzone, controls RhoA activity at the equatorial cortex during anaphase is not understood. Here, we show that Ect2 concentrates at the equatorial membrane during cytokinesis in live cells. Ect2 membrane association requires a pleckstrin homology domain and a polybasic cluster that bind to phosphoinositide lipids. Both guanine nucleotide exchange function and membrane targeting of Ect2 are essential for RhoA activation and cleavage furrow formation in human cells. Membrane localization of Ect2 is spatially confined to the equator by centralspindlin, Ect2's spindle midzone anchor complex, and is temporally coordinated with chromosome segregation through the activation state of CDK1. We propose that targeting of Ect2 to the equatorial membrane represents a key step in the delivery of the cytokinetic signal to the cortex.
authors.affiliation: Cell Division and Aneuploidy Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK.
authors.forename: Kuan-Chung
authors.initials: KC
authors.lastname: Su
authors.forename: Tohru
authors.initials: T
authors.lastname: Takaki
authors.forename: Mark
authors.initials: M
authors.lastname: Petronczki
mesh_terms: D000705:Anaphase / Q000235:genetics / Q000502:physiology; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D048749:Cytokinesis / Q000502:physiology*; D020662:Guanine Nucleotide Exchange Factors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D054730:Protein Interaction Domains and Motifs; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D064067:Rho Guanine Nucleotide Exchange Factors; D008941:Spindle Apparatus / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: C489850:ECT2 protein, human; D020662:Guanine Nucleotide Exchange Factors; D011518:Proto-Oncogene Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; C066737:RHOA protein, human; D016203:CDC2 Protein Kinase; D020742:rhoA GTP-Binding Protein