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TheConservedKMNNetworkConstitutes the Core Microtubule-Binding Site of the Kinetochore



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The Conserved KMN Network Constitutes the Core Microtubule Binding Site of the Kinetochore Iain M Cheeseman 1 Joshua S Chappie 2 Elizabeth M Wilson Kubalek 2 and Arshad Desai1 1 Ludwig Institute for Cancer Research Department of Cellular and Molecular Medicine UCSD CMM East Room 3052 La Jolla CA 92093 USA 2 Center for Integrative Molecular Biosciences Department of Cell Biology The Scripps Research Institute 10550 North Torrey Pines Road La Jolla CA 92037 USA Contact icheeseman ucsd edu I M C abdesai ucsd edu A D DOI 10 1016 j cell 2006 09 039 SUMMARY The microtubule binding interface of the kinetochore is of central importance in chromosome segregation Although kinetochore components that stabilize translocate on and affect the polymerization state of microtubules have been identified none have proven essential for kinetochore microtubule interactions Here we examined the conserved KNL 1 Mis12 complex Ndc80 complex KMN network which is essential for kinetochore microtubule interactions in vivo We identified two distinct microtubule binding activities within the KMN network one associated with the Ndc80 Nuf2 subunits of the Ndc80 complex and a second in KNL 1 Formation of the complete KMN network which additionally requires the Mis12 complex and the Spc24 Spc25 subunits of the Ndc80 complex synergistically enhances microtubulebinding activity Phosphorylation by Aurora B which corrects improper kinetochore microtubule connections in vivo reduces the affinity of the Ndc80 complex for microtubules in vitro Based on these findings we propose that the conserved KMN network constitutes the core microtubule binding site of the kinetochore INTRODUCTION In the late nineteenth century a differentiated chromosomal region that connects to spindle fibers during mitosis was first described reviewed in Schrader 1953 Electron microscopy provided a direct view of this region termed the kinetochore and demonstrated that microtubule plus ends directly embed in the outer kinetochore



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