title: An anillin-Ect2 complex stabilizes central spindle microtubules at the cortex during cytokinesis.
abstract: Cytokinesis occurs due to the RhoA-dependent ingression of an actomyosin ring. During anaphase, the Rho GEF (guanine nucleotide exchange factor) Ect2 is recruited to the central spindle via its interaction with MgcRacGAP/Cyk-4, and activates RhoA in the central plane of the cell. Ect2 also localizes to the cortex, where it has access to RhoA. The N-terminus of Ect2 binds to Cyk-4, and the C-terminus contains conserved DH (Dbl homologous) and PH (Pleckstrin Homology) domains with GEF activity. The PH domain is required for Ect2's cortical localization, but its molecular function is not known. In cultured human cells, we found that the PH domain interacts with anillin, a contractile ring protein that scaffolds actin and myosin and interacts with RhoA. The anillin-Ect2 interaction may require Ect2's association with lipids, since a novel mutation in the PH domain, which disrupts phospholipid association, weakens their interaction. An anillin-RacGAP50C (homologue of Cyk-4) complex was previously described in Drosophila, which may crosslink the central spindle to the cortex to stabilize the position of the contractile ring. Our data supports an analogous function for the anillin-Ect2 complex in human cells and one hypothesis is that this complex has functionally replaced the Drosophila anillin-RacGAP50C complex. Complexes between central spindle proteins and cortical proteins could regulate the position of the contractile ring by stabilizing microtubule-cortical interactions at the division plane to ensure the generation of active RhoA in a discrete zone.
authors.affiliation: Department of Biology, Concordia University, Montreal, Quebec, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Frenette
authors.forename: Eric
authors.initials: E
authors.lastname: Haines
authors.forename: Michael
authors.initials: M
authors.lastname: Loloyan
authors.forename: Mena
authors.initials: M
authors.lastname: Kinal
authors.forename: Paknoosh
authors.initials: P
authors.lastname: Pakarian
authors.forename: Alisa
authors.initials: A
authors.lastname: Piekny
mesh_terms: D000818:Animals; D002460:Cell Line; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism*; D048749:Cytokinesis / Q000235:genetics / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D003285:Contractile Proteins; D029721:Drosophila Proteins; C489850:ECT2 protein, human; D020662:Guanine Nucleotide Exchange Factors; C121865:Pbl protein, Drosophila; D011518:Proto-Oncogene Proteins; C095886:anillin