NDLI: Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly

Content Provider	PubMed Central
Author	Chan, Ying Wai Fava, Luca L. Andreas, Uldschmid Schmitz, Michael H. A. Gerlich, Daniel W. Nigg, Erich A. Santamaria, Anna
Copyright Year	2009
Abstract	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.
Related Links	http://dx.doi.org/10.1083/jcb.200812167
Ending Page	874
Page Count	16
Starting Page	859
File Format	PDF
ISSN	00219525
e-ISSN	15408140
Journal	The Journal of Cell Biology
Issue Number	5
Volume Number	185
Language	English
Publisher	The Rockefeller University Press
Publisher Date	2009-06-01
Access Restriction	Open
Rights Holder	The Rockefeller University Press
Subject Keyword	Cell Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine

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Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly

Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore

Cytoplasmic dynein/dynactin drives kinetochore protein transport to the spindle poles and has a role in mitotic spindle checkpoint inactivation

Dynein light chain 1 and a spindle-associated adaptor promote dynein asymmetry and spindle orientation

Clustering of cortical dynein regulates the mechanics of spindle orientation in human mitotic cells

Microtubule-dependent path to the cell cortex for cytoplasmic dynein in mitotic spindle orientation

Requirement of the Dynein-adaptor Spindly for mitotic and post-mitotic functions in Drosophila

Preventing farnesylation of the dynein adaptor Spindly contributes to the mitotic defects caused by farnesyltransferase inhibitors

Antagonism between the dynein and Ndc80 complexes at kinetochores controls the stability of kinetochore–microtubule attachments during mitosis

Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly

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Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly

Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore

Cytoplasmic dynein/dynactin drives kinetochore protein transport to the spindle poles and has a role in mitotic spindle checkpoint inactivation

Dynein light chain 1 and a spindle-associated adaptor promote dynein asymmetry and spindle orientation

Clustering of cortical dynein regulates the mechanics of spindle orientation in human mitotic cells

Microtubule-dependent path to the cell cortex for cytoplasmic dynein in mitotic spindle orientation

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Mitotic control of kinetochore-associated dynein and spindle orientation by human Spindly