title: Plasma Membrane Association but Not Midzone Recruitment of RhoGEF ECT2 Is Essential for Cytokinesis.
abstract: Cytokinesis, the final step of cell division, begins with the formation of a cleavage furrow. How the mitotic spindle specifies the furrow at the equator in animal cells remains unknown. Current models propose that the concentration of the RhoGEF ECT2 at the spindle midzone and the equatorial plasma membrane directs furrow formation. Using chemical genetic and optogenetic tools, we demonstrate that the association of ECT2 with the plasma membrane during anaphase is required and sufficient for cytokinesis. Local membrane targeting of ECT2 leads to unilateral furrowing, highlighting the importance of local ECT2 activity. ECT2 mutations that prevent centralspindlin binding compromise concentration of ECT2 at the midzone and equatorial membrane but sustain cytokinesis. While the association of ECT2 with the plasma membrane is essential for cytokinesis, our data suggest that ECT2 recruitment to the spindle midzone is insufficient to account for equatorial furrowing and may act redundantly with yet-uncharacterized signals.
authors.affiliation: Cell Division and Aneuploidy Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Herts EN6 3LD, UK; DNA Recombination and Repair Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Kristýna
authors.initials: K
authors.lastname: Kotýnková
authors.affiliation: Cell Division and Aneuploidy Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Herts EN6 3LD, UK; Whitehead Institute and Department of Biology, MIT, 9 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Kuan-Chung
authors.initials: KC
authors.lastname: Su
authors.affiliation: DNA Recombination and Repair Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: West
authors.affiliation: Cell Division and Aneuploidy Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Herts EN6 3LD, UK; Boehringer Ingelheim RCV, Dr.-Boehringer-Gasse 5-11, 1121 Vienna, Austria. Electronic address: mark_paul.petronczki@boehringer-ingelheim.com.
authors.forename: Mark
authors.initials: M
authors.lastname: Petronczki
mesh_terms: D000705:Anaphase / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics* / Q000378:metabolism; D048749:Cytokinesis / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D008941:Spindle Apparatus / Q000235:genetics
chemical_list: C489850:ECT2 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins
keywords: cell division; chemical genetics; cleavage plane; contractile ring; cytokinesis; cytoskeleton; mitosis; optogenetics; plasma membrane; spindle midzone