Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly
| Autor: | Andreas Uldschmid, Michael H.A. Schmitz, Luca L. Fava, Anna Santamaria, Daniel W. Gerlich, Ying Wai Chan, Erich A. Nigg |
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| Rok vydání: | 2009 |
| Předmět: |
Mad2
Paclitaxel Dynein Mitosis Spindle Apparatus macromolecular substances Protein Serine-Threonine Kinases Biology Article Chromosome segregation Aurora Kinases Aurora Kinase B Chromosomes Human Humans Prometaphase Kinetochores Research Articles Kinetochore Dyneins Nuclear Proteins Dynactin Complex Cell Biology Cell biology Spindle apparatus Cytoskeletal Proteins ZW10 Microtubule-Associated Proteins HeLa Cells Signal Transduction |
| Zdroj: | The Journal of Cell Biology The Journal of Cell Biology, 185 (5) |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Mitotic spindle formation and chromosome segregation depend critically on kinetochore–microtubule (KT–MT) interactions. A new protein, termed Spindly in Drosophila and SPDL-1 in C. elegans, was recently shown to regulate KT localization of dynein, but depletion phenotypes revealed striking differences, suggesting evolutionarily diverse roles of mitotic dynein. By characterizing the function of Spindly in human cells, we identify specific functions for KT dynein. We show that localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B. hSpindly depletion results in reduced inter-KT tension, unstable KT fibers, an extensive prometaphase delay, and severe chromosome misalignment. Moreover, depletion of hSpindly induces a striking spindle rotation, which can be rescued by co-depletion of dynein. However, in contrast to Drosophila, hSpindly depletion does not abolish the removal of MAD2 and ZW10 from KTs. Collectively, our data reveal hSpindly-mediated dynein functions and highlight a critical role of KT dynein in spindle orientation. The Journal of Cell Biology, 185 (5) ISSN:0021-9525 ISSN:1540-8140 |
| Databáze: | OpenAIRE |
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