KNL1 and the CENP-H/I/K complex coordinately direct kinetochore assembly in vertebrates.
Chromosome segregation during mitosis requires the assembly of a large proteinaceous structure termed the kinetochore. In Caenorhabditis elegans, KNL-1 is required to target multiple outer kinetochore proteins. Here, we demonstrate that the vertebrate KNL1 counterpart is essential for chromosome segregation and is required to localize a subset of outer kinetochore proteins. However, unlike in C. elegans, depletion of vertebrate KNL1 does not abolish kinetochore localization of the microtubule-binding Ndc80 complex. Instead, we show that KNL1 and CENP-K, a subunit of a constitutively centromere-associated complex that is missing from C. elegans, coordinately direct Ndc80 complex localization. Simultaneously reducing both hKNL1 and CENP-K function abolishes all aspects of kinetochore assembly downstream of centromeric chromatin and causes catastrophic chromosome segregation defects. These findings explain discrepancies in kinetochore assembly pathways between different organisms and reveal a surprising plasticity in the assembly mechanism of an essential cell division organelle.
Ludwig Institute for Cancer Research, and Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA. icheese@wi.mit.edu
Iain M
IM
Cheeseman
Tetsuya
T
Hori
Tatsuo
T
Fukagawa
Arshad
A
Desai
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002645:Chickens; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D045584:Chromosome Positioning; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000378:metabolism*; D008938:Mitosis; D008954:Models, Biological; D009687:Nuclear Proteins / Q000172:deficiency / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D014714:Vertebrates / Q000378:metabolism*
C121933:CENPH protein, human; C484297:CENPI protein, human; C102640:CENPK protein, human; D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C472643:Knl1 protein, human; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; C120529:NDC80 protein, human; D009687:Nuclear Proteins; C413695:ZWINT protein, human; C094772:centromere protein F