title: Citron kinase controls abscission through RhoA and anillin.
abstract: The small GTPase RhoA plays a crucial role in the different stages of cytokinesis, including contractile ring formation, cleavage furrow ingression, and midbody abscission. Citron kinase (CIT-K), a protein required for cytokinesis and conserved from insects to mammals, is currently considered a cytokinesis-specific effector of active RhoA. In agreement with previous observations, we show here that, as in Drosophila cells, CIT-K is specifically required for abscission in mammalian cells. However, in contrast with the current view, we provide evidence that CIT-K is an upstream regulator rather than a downstream effector of RhoA during late cytokinesis. In addition, we show that CIT-K is capable of physically and functionally interacting with the actin-binding protein anillin. Active RhoA and anillin are displaced from the midbody in CIT-K-depleted cells, while only anillin, but not CIT-K, is affected if RhoA is inactivated in late cytokinesis. The overexpression of CIT-K and of anillin leads to abscission delay. However, the delay produced by CIT-K overexpression can be reversed by RhoA inactivation, while the delay produced by anillin overexpression is RhoA-independent. Altogether, these results indicate that CIT-K is a crucial abscission regulator that may promote midbody stability through active RhoA and anillin.
authors.affiliation: Department of Genetics, Biology, and Biochemistry, Molecular Biotechnology Center, University of Turin, 10126 Turin, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Gai
authors.forename: Paola
authors.initials: P
authors.lastname: Camera
authors.forename: Alessandro
authors.initials: A
authors.lastname: Dema
authors.forename: Federico
authors.initials: F
authors.lastname: Bianchi
authors.forename: Gaia
authors.initials: G
authors.lastname: Berto
authors.forename: Elena
authors.initials: E
authors.lastname: Scarpa
authors.forename: Giulia
authors.initials: G
authors.lastname: Germena
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Di Cunto
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism*; D048749:Cytokinesis / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D003285:Contractile Proteins; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C095886:anillin; C066737:RHOA protein, human; C115635:citron-kinase; D017346:Protein Serine-Threonine Kinases; D020742:rhoA GTP-Binding Protein