Phosphorylation-dependent protein interactions at the spindle midzone mediate cell cycle regulation of spindle elongation - PubMed (original) (raw)
Phosphorylation-dependent protein interactions at the spindle midzone mediate cell cycle regulation of spindle elongation
Anton Khmelinskii et al. Dev Cell. 2009 Aug.
Free article
Abstract
The metaphase-to-anaphase transition is one of the most dramatic and highly regulated steps in cell division. At anaphase onset the protease separase dissolves sister chromatid cohesion. Simultaneously, the mitotic spindle elongates as interpolar microtubules (iMTs) slide apart at the spindle midzone, ensuring chromosome segregation. However, it remains unclear how spindle elongation is coordinated with cell cycle progression. Here we demonstrate that phosphorylation of the midzone organizer Ase1 controls localization and function of Cin8, a kinesin-5 that slides iMTs relative to each other. Phosphorylation of Ase1 by Cdk1 (cyclin-dependent kinase) inhibits Cin8 binding to iMTs, preventing bending and collapse of the metaphase spindle. In anaphase Ase1 dephosphorylation by the separase-activated phosphatase Cdc14 is necessary and sufficient for Cin8 recruitment to the midzone, where it drives spindle elongation. Our results reveal that sliding forces at the midzone are activated by separase and explain how spindle elongation is triggered with anaphase entry.
Similar articles
- Assembling the spindle midzone in the right place at the right time.
Khmelinskii A, Schiebel E. Khmelinskii A, et al. Cell Cycle. 2008 Feb 1;7(3):283-6. doi: 10.4161/cc.7.3.5349. Epub 2007 Nov 21. Cell Cycle. 2008. PMID: 18235228 Review. - Phospho-regulated interaction between kinesin-6 Klp9p and microtubule bundler Ase1p promotes spindle elongation.
Fu C, Ward JJ, Loiodice I, Velve-Casquillas G, Nedelec FJ, Tran PT. Fu C, et al. Dev Cell. 2009 Aug;17(2):257-67. doi: 10.1016/j.devcel.2009.06.012. Dev Cell. 2009. PMID: 19686686 Free PMC article. - Phospho-regulation of kinesin-5 during anaphase spindle elongation.
Avunie-Masala R, Movshovich N, Nissenkorn Y, Gerson-Gurwitz A, Fridman V, Kõivomägi M, Loog M, Hoyt MA, Zaritsky A, Gheber L. Avunie-Masala R, et al. J Cell Sci. 2011 Mar 15;124(Pt 6):873-8. doi: 10.1242/jcs.077396. J Cell Sci. 2011. PMID: 21378308 Free PMC article. - Ase1 domains dynamically slow anaphase spindle elongation and recruit Bim1 to the midzone.
Thomas EC, Ismael A, Moore JK. Thomas EC, et al. Mol Biol Cell. 2020 Nov 15;31(24):2733-2747. doi: 10.1091/mbc.E20-07-0493-T. Epub 2020 Sep 30. Mol Biol Cell. 2020. PMID: 32997572 Free PMC article. - Factors that Control Mitotic Spindle Dynamics.
Fraschini R. Fraschini R. Adv Exp Med Biol. 2017;925:89-101. doi: 10.1007/5584_2016_74. Adv Exp Med Biol. 2017. PMID: 27722958 Review.
Cited by
- DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci.
Ayra-Plasencia J, Machín F. Ayra-Plasencia J, et al. Nat Commun. 2019 Jun 28;10(1):2862. doi: 10.1038/s41467-019-10742-8. Nat Commun. 2019. PMID: 31253793 Free PMC article. - An in vitro Microscopy-based Assay for Microtubule-binding and Microtubule-crosslinking by Budding Yeast Microtubule-associated Protein.
Zhu Y, Tan W, Lee WL. Zhu Y, et al. Bio Protoc. 2018 Dec 5;8(23):e3110. doi: 10.21769/BioProtoc.3110. Bio Protoc. 2018. PMID: 30733975 Free PMC article. - The kinesin-8 Kip3 scales anaphase spindle length by suppression of midzone microtubule polymerization.
Rizk RS, Discipio KA, Proudfoot KG, Gupta ML Jr. Rizk RS, et al. J Cell Biol. 2014 Mar 17;204(6):965-75. doi: 10.1083/jcb.201312039. Epub 2014 Mar 10. J Cell Biol. 2014. PMID: 24616221 Free PMC article. - Ipl1/Aurora-dependent phosphorylation of Sli15/INCENP regulates CPC-spindle interaction to ensure proper microtubule dynamics.
Nakajima Y, Cormier A, Tyers RG, Pigula A, Peng Y, Drubin DG, Barnes G. Nakajima Y, et al. J Cell Biol. 2011 Jul 11;194(1):137-53. doi: 10.1083/jcb.201009137. Epub 2011 Jul 4. J Cell Biol. 2011. PMID: 21727193 Free PMC article. - Chromatids segregate without centrosomes during Caenorhabditis elegans mitosis in a Ran- and CLASP-dependent manner.
Nahaboo W, Zouak M, Askjaer P, Delattre M. Nahaboo W, et al. Mol Biol Cell. 2015 Jun 1;26(11):2020-9. doi: 10.1091/mbc.E14-12-1577. Epub 2015 Apr 1. Mol Biol Cell. 2015. PMID: 25833711 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous