Phosphorylation relieves autoinhibition of the kinetochore motor Cenp-E.
During mitosis, chromosome alignment depends on the regulated dynamics of microtubules and on motor protein activities. At the kinetochore, the interplay between microtubule-binding proteins, motors, and kinases is poorly understood. Cenp-E is a kinetochore-associated kinesin involved in chromosome congression, but the mechanism by which this is achieved is unclear. Here, we present a study of the regulation of Cenp-E motility by using purified full-length (FL) Xenopus Cenp-E protein, which demonstrates that FL Cenp-E is a genuine plus-end-directed motor. Furthermore, we find that the Cenp-E tail completely blocks the motility of Cenp-E in vitro. This is achieved through direct interaction between its motor and tail domains. Finally, we show that Cenp-E autoinhibition is reversed by MPS1- or CDK1-cyclin B-mediated phosphorylation of the Cenp-E tail. This suggests a model of dynamic control of Cenp-E motility, and hence chromosome congression, dependent upon phosphorylation at the kinetochore.
Espeut
Julien
J
Universités Montpellier 2 et 1, IFR122, CRBM, 34293 Montpellier, France; CNRS, UMR 5237, 1919 Route de Mende, 34293 Montpellier, France.
Gaussen
Amaury
A
Bieling
Peter
P
Morin
Violeta
V
Prieto
Susana
S
Fesquet
Didier
D
Surrey
Thomas
T
Abrieu
Ariane
A
D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D002868:Chromosomal Proteins, Non-Histone; D020409:Molecular Motor Proteins; D029867:Xenopus Proteins; C068688:centromere protein E