title: Timely Endocytosis of Cytokinetic Enzymes Prevents Premature Spindle Breakage during Mitotic Exit.
abstract: Cytokinesis requires the spatio-temporal coordination of membrane deposition and primary septum (PS) formation at the division site to drive acto-myosin ring (AMR) constriction. It has been demonstrated that AMR constriction invariably occurs only after the mitotic spindle disassembly. It has also been established that Chitin Synthase II (Chs2p) neck localization precedes mitotic spindle disassembly during mitotic exit. As AMR constriction depends upon PS formation, the question arises as to how chitin deposition is regulated so as to prevent premature AMR constriction and mitotic spindle breakage. In this study, we propose that cells regulate the coordination between spindle disassembly and AMR constriction via timely endocytosis of cytokinetic enzymes, Chs2p, Chs3p, and Fks1p. Inhibition of endocytosis leads to over accumulation of cytokinetic enzymes during mitotic exit, which accelerates the constriction of the AMR, and causes spindle breakage that eventually could contribute to monopolar spindle formation in the subsequent round of cell division. Intriguingly, the mitotic spindle breakage observed in endocytosis mutants can be rescued either by deleting or inhibiting the activities of, CHS2, CHS3 and FKS1, which are involved in septum formation. The findings from our study highlight the importance of timely endocytosis of cytokinetic enzymes at the division site in safeguarding mitotic spindle integrity during mitotic exit.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Cheen Fei
authors.identifier: 0000-0001-6753-9228
authors.initials: CF
authors.lastname: Chin
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Kaiquan
authors.identifier: 0000-0002-7530-168X
authors.initials: K
authors.lastname: Tan
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Onishi
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: YuanYuan
authors.identifier: 0000-0002-6116-5330
authors.initials: Y
authors.lastname: Chew
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Beryl
authors.identifier: 0000-0002-2937-7798
authors.initials: B
authors.lastname: Augustine
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Wei Ren
authors.identifier: 0000-0003-2498-238X
authors.initials: WR
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Foong May
authors.initials: FM
authors.lastname: Yeong
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D002462:Cell Membrane / Q000235:genetics; D002686:Chitin / Q000235:genetics; D002687:Chitin Synthase / Q000235:genetics*; D048749:Cytokinesis / Q000235:genetics; D054714:Echinocandins / Q000235:genetics*; D004705:Endocytosis / Q000235:genetics*; D005964:Glucosyltransferases / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000235:genetics*; D015879:Myosin Subfragments / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D008941:Spindle Apparatus / Q000235:genetics
chemical_list: D054714:Echinocandins; D008565:Membrane Proteins; D015879:Myosin Subfragments; D029701:Saccharomyces cerevisiae Proteins; D002686:Chitin; D005964:Glucosyltransferases; C069390:CHS3 protein, S cerevisiae; D002687:Chitin Synthase; C582195:Chs2 protein, S cerevisiae; C091618:FKS1 protein, S cerevisiae