Regulation of Outer Kinetochore Ndc80 Complex-Based Microtubule
Regulation of outer kinetochore Ndc80 complex-based PNAS PLUS microtubule attachments by the central kinetochore Mis12/MIND complex Emily M. Kudalkara,1, Emily A. Scarborougha, Neil T. Umbreita,2, Alex Zeltera, Daniel R. Gestauta,3, Michael Rifflea, Richard S. Johnsonb, Michael J. MacCossb, Charles L. Asburyc, and Trisha N. Davisa,4 aDepartment of Biochemistry, University of Washington, Seattle, WA 98195; bDepartment of Genome Sciences, University of Washington, Seattle, WA 98195; and cDepartment of Physiology and Biophysics, University of Washington, Seattle, WA 98195 Edited by Edward D. Korn, National Heart, Lung and Blood Institute, Bethesda, MD, and approved August 26, 2015 (received for review July 15, 2015) Multiple protein subcomplexes of the kinetochore cooperate as a Spc105, Mis12/MIND (Mtw1, Nsl1, Nnf1, Dsn1) complex, and cohesive molecular unit that forms load-bearing microtubule attach- Ndc80 (Ndc80, Nuf2, Spc24, Spc25) complex (5). In C. elegans, ments that drive mitotic chromosome movements. There is intriguing the 4-protein Ndc80 complex and Knl1 bind directly to micro- evidence suggesting that central kinetochore components influence tubules, but MIND does not. Instead, MIND serves as a struc- kinetochore–microtubule attachment, but the mechanism remains tural linker that connects DNA-binding components with the unclear. Here, we find that the conserved Mis12/MIND (Mtw1, microtubule-binding complexes (6, 7). The KMN complex binds Nsl1, Nnf1, Dsn1) and Ndc80 (Ndc80, Nuf2, Spc24, Spc25) com- microtubules with a higher affinity than Ndc80 complex or Knl1 plexes are connected by an extensive network of contacts, each alone, demonstrating that MIND can facilitate the synergistic essential for viability in cells, and collectively able to withstand sub- binding of outer kinetochore complexes.
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