Dynamic distribution of TTK in HeLa cells: insights from an ultrastructural study.
Entry into mitosis is driven by signaling cascades of mitotic kinases. Our recent studies show that TTK, a kinetochore-associated protein kinase, interacts with CENP-E, a mitotic kinesin located to corona fiber of kinetochore. Using immunoelectron microscopy, here we show that TTK is present at the nuclear pore adjacent complex of interphase HeLa cells. Upon nuclear envelope fragmentation, TTK targets to the outermost region of the developing kinetochores of monoorient chromosome as well as to spindle poles. After stable attachment, throughout chromosome congression, TTK is a constituent of the corona fibers, extending up to 90 nm away from the kinetochore outer plate. Upon metaphase alignment, TTK departs from the kinetochore and migrates toward the centrosomes. Taken together, this evidence strongly supports a model in which TTK functions in spindle checkpoint signaling cascades at both kinetochore and centrosome.
Dou
Zhen
Z
Laboratory of Cell Dynamics, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China.
Sawagechi
Akira
A
Zhang
Jie
J
Luo
Hong
H
Brako
Lawrence
L
Yao
Xue Biao
XB
D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000648:ultrastructure*; D018385:Centrosome / Q000378:metabolism / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism / Q000648:ultrastructure; D002875:Chromosomes / Q000378:metabolism / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron; D008938:Mitosis; D008954:Models, Biological; D022022:Nuclear Pore / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D011494:Protein Kinases / Q000378:metabolism* / Q000648:ultrastructure*; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C068688:centromere protein E; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human