TY - JOUR
T1 - Kinetochore-dependent microtubule rescue ensures their efficient and sustained interactions in early mitosis
AU - Gandhi, Sapan R.
AU - Gierliński, Marek
AU - Mino, Akihisa
AU - Tanaka, Kozo
AU - Kitamura, Etsushi
AU - Clayton, Lesley
AU - Tanaka, Tomoyuki U.
N1 - Funding Information:
We thank J. Howard and all Tanaka lab members for helpful discussions; G. Barton for supervising the Data Analysis Group; K. Kitada for detailed replication profile in budding yeast; S. Komoto and C. Antony for electron tomography images used to determine parameter values for the computer simulation; C. Allan, N. Kobayashi, and S. Swift for help on microscopy and computing; K. Nasmyth, E. Schiebel, J.E. Haber, R. Tsien, J. Naismyth, W.K. Huh, K.E. Sawin, Yeast Resource Centre, and EUROSCARF for reagents; and E. Gandhi for copyediting the manuscript. This work was supported by Association for International Cancer Research, Wellcome Trust, Cancer Research UK, Human Frontier Science Program, Medical Research Council, and Lister Research Institute Prize. S.R.G. was supported by the Nicoll Lindsay studentship and the Overseas Research Students Awards. T.U.T. is a Senior Research Fellow of Cancer Research UK.
PY - 2011/11/15
Y1 - 2011/11/15
N2 - How kinetochores regulate microtubule dynamics to ensure proper kinetochore-microtubule interactions is unknown. Here, we studied this during early mitosis in Saccharomyces cerevisiae. When a microtubule shrinks and its plus end reaches a kinetochore bound to its lateral surface, the microtubule end attempts to tether the kinetochore. This process often fails and, responding to this failure, microtubule rescue (conversion from shrinkage to growth) occurs, preventing kinetochore detachment from the microtubule end. This rescue is promoted by Stu2 transfer (ortholog of vertebrate XMAP215/ch-TOG) from the kinetochore to the microtubule end. Meanwhile, microtubule rescue distal to the kinetochore is also promoted by Stu2, which is transported by a kinesin-8 motor Kip3 along the microtubule from the kinetochore. Microtubule extension following rescue facilitates interaction with other widely scattered kinetochores, diminishing long delays in collecting the complete set of kinetochores by microtubules. Thus, kinetochore-dependent microtubule rescue ensures efficient and sustained kinetochore-microtubule interactions in early mitosis.
AB - How kinetochores regulate microtubule dynamics to ensure proper kinetochore-microtubule interactions is unknown. Here, we studied this during early mitosis in Saccharomyces cerevisiae. When a microtubule shrinks and its plus end reaches a kinetochore bound to its lateral surface, the microtubule end attempts to tether the kinetochore. This process often fails and, responding to this failure, microtubule rescue (conversion from shrinkage to growth) occurs, preventing kinetochore detachment from the microtubule end. This rescue is promoted by Stu2 transfer (ortholog of vertebrate XMAP215/ch-TOG) from the kinetochore to the microtubule end. Meanwhile, microtubule rescue distal to the kinetochore is also promoted by Stu2, which is transported by a kinesin-8 motor Kip3 along the microtubule from the kinetochore. Microtubule extension following rescue facilitates interaction with other widely scattered kinetochores, diminishing long delays in collecting the complete set of kinetochores by microtubules. Thus, kinetochore-dependent microtubule rescue ensures efficient and sustained kinetochore-microtubule interactions in early mitosis.
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U2 - 10.1016/j.devcel.2011.09.006
DO - 10.1016/j.devcel.2011.09.006
M3 - Article
C2 - 22075150
AN - SCOPUS:80755129124
VL - 21
SP - 920
EP - 933
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 5
ER -