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.
Cheeseman
Iain M
IM
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
Hori
Tetsuya
T
Fukagawa
Tatsuo
T
Desai
Arshad
A
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