Crosstalk between microtubule attachment complexes ensures accurate chromosome segregation.
The microtubule-based mitotic spindle segregates chromosomes during cell division. During chromosome segregation, the centromeric regions of chromosomes build kinetochores that establish end-coupled attachments to spindle microtubules. Here, we used the Caenorhabditis elegans embryo as a model system to examine the crosstalk between two kinetochore protein complexes implicated in temporally distinct stages of attachment formation. The kinetochore dynein module, which mediates initial lateral microtubule capture, inhibited microtubule binding by the Ndc80 complex, which ultimately forms the end-coupled attachments that segregate chromosomes. The kinetochore dynein module directly regulated Ndc80, independently of phosphorylation by Aurora B kinase, and this regulation was required for accurate segregation. Thus, the conversion from initial dynein-mediated, lateral attachments to correctly oriented, Ndc80-mediated end-coupled attachments is actively controlled.
Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Dhanya K
DK
Cheerambathur
Reto
R
Gassmann
Brian
B
Cook
Karen
K
Oegema
Arshad
A
Desai
D020816:Amino Acid Motifs; D000818:Animals; D064107:Aurora Kinase B / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000196:embryology; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D004398:Dyneins / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation; D011485:Protein Binding; D008941:Spindle Apparatus / Q000378:metabolism*; D019076:Transgenes
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; C492665:NDC-80 protein, C elegans; C532870:SPDL-1 protein, C elegans; D064107:Aurora Kinase B; D004398:Dyneins