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• W2912891864 abstract "Each time a cell divides, the microtubule cytoskeleton self-organizes into the metaphase spindle: an ellipsoidal steady-state structure that holds its stereotyped geometry despite microtubule turnover and internal stresses [1Saxton W.M. Stemple D.L. Leslie R.J. Salmon E.D. Zavortink M. McIntosh J.R. Tubulin dynamics in cultured mammalian cells.J. Cell Biol. 1984; 99: 2175-2186Crossref PubMed Scopus (331) Google Scholar, 2Gorbsky G.J. Simerly C. Schatten G. Borisy G.G. Microtubules in the metaphase-arrested mouse oocyte turn over rapidly.Proc. Natl. Acad. Sci. USA. 1990; 87: 6049-6053Crossref PubMed Scopus (45) Google Scholar, 3Dumont S. Mitchison T.J. Force and length in the mitotic spindle.Curr. Biol. 2009; 19: R749-R761Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar, 4McIntosh J.R. Molodtsov M.I. Ataullakhanov F.I. Biophysics of mitosis.Q. Rev. Biophys. 2012; 45: 147-207Crossref PubMed Scopus (93) Google Scholar, 5Brugués J. Needleman D. Physical basis of spindle self-organization.Proc. Natl. Acad. Sci. USA. 2014; 111: 18496-18500Crossref PubMed Scopus (100) Google Scholar, 6Oriola D. Needleman D.J. Brugués J. The physics of the metaphase spindle.Annu. Rev. Biophys. 2018; 47: 655-673Crossref PubMed Scopus (29) Google Scholar]. Regulation of microtubule dynamics, motor proteins, microtubule crosslinking, and chromatid cohesion can modulate spindle size and shape, and yet modulated spindles reach and hold a new steady state [7Goshima G. Wollman R. Stuurman N. Scholey J.M. Vale R.D. Length control of the metaphase spindle.Curr. Biol. 2005; 15: 1979-1988Abstract Full Text Full Text PDF PubMed Scopus (209) Google Scholar, 8Goshima G. Scholey J.M. Control of mitotic spindle length.Annu. Rev. Cell Dev. Biol. 2010; 26: 21-57Crossref PubMed Scopus (158) Google Scholar, 9Helmke K.J. Heald R. Wilbur J.D. Interplay between spindle architecture and function.Int. Rev. Cell Mol. Biol. 2013; 306: 83-125Crossref PubMed Scopus (58) Google Scholar, 10Crowder M.E. Strzelecka M. Wilbur J.D. Good M.C. von Dassow G. Heald R. A comparative analysis of spindle morphometrics across metazoans.Curr. Biol. 2015; 25: 1542-1550Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar, 11Farhadifar R. Baer C.F. Valfort A.C. Andersen E.C. Müller-Reichert T. Delattre M. Needleman D.J. Scaling, selection, and evolutionary dynamics of the mitotic spindle.Curr. Biol. 2015; 25: 732-740Abstract Full Text Full Text PDF PubMed Scopus (51) Google Scholar]. Here, we ask what maintains any spindle steady-state geometry. We report that clustering of microtubule ends by dynein and NuMA is essential for mammalian spindles to hold a steady-state shape. After dynein or NuMA deletion, the mitotic microtubule network is “turbulent”; microtubule bundles extend and bend against the cell cortex, constantly remodeling network shape. We find that spindle turbulence is driven by the homotetrameric kinesin-5 Eg5, and that acute Eg5 inhibition in turbulent spindles recovers spindle geometry and stability. Inspired by in vitro work on active turbulent gels of microtubules and kinesin [12Sanchez T. Chen D.T.N. DeCamp S.J. Heymann M. Dogic Z. Spontaneous motion in hierarchically assembled active matter.Nature. 2012; 491: 431-434Crossref PubMed Scopus (892) Google Scholar, 13DeCamp S.J. Redner G.S. Baskaran A. Hagan M.F. Dogic Z. Orientational order of motile defects in active nematics.Nat. Mater. 2015; 14: 1110-1115Crossref PubMed Scopus (206) Google Scholar], we explore the kinematics of this in vivo turbulent network. We find that turbulent spindles display decreased nematic order and that motile asters distort the nematic director field. Finally, we see that turbulent spindles can drive both flow of cytoplasmic organelles and whole-cell movement—analogous to the autonomous motility displayed by droplet-encapsulated turbulent gels [12Sanchez T. Chen D.T.N. DeCamp S.J. Heymann M. Dogic Z. Spontaneous motion in hierarchically assembled active matter.Nature. 2012; 491: 431-434Crossref PubMed Scopus (892) Google Scholar]. Thus, end-clustering by dynein and NuMA is required for mammalian spindles to reach a steady-state geometry, and in their absence Eg5 powers a turbulent microtubule network inside mitotic cells." @default.
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• W2912891864 date "2019-02-01" @default.
• W2912891864 modified "2023-10-13" @default.
• W2912891864 title "Microtubule End-Clustering Maintains a Steady-State Spindle Shape" @default.
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• W2912891864 doi "https://doi.org/10.1016/j.cub.2019.01.016" @default.
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