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Kinetochore–microtubule attachment throughout mitosis potentiated by the elongated stalk of the kinetochore kinesin CENP-E

Centromere protein E (CENP-E) is a highly elongated kinesin that transports pole-proximal chromosomes during congression in prometaphase. During metaphase, it facilitates kinetochore–microtubule end-on attachment required to achieve and maintain chromosome alignment. In vitro CENP-E can walk process...

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Autores principales: Vitre, Benjamin, Gudimchuk, Nikita, Borda, Ranier, Kim, Yumi, Heuser, John E., Cleveland, Don W., Grishchuk, Ekaterina L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116301/
https://www.ncbi.nlm.nih.gov/pubmed/24920822
http://dx.doi.org/10.1091/mbc.E14-01-0698
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author Vitre, Benjamin
Gudimchuk, Nikita
Borda, Ranier
Kim, Yumi
Heuser, John E.
Cleveland, Don W.
Grishchuk, Ekaterina L.
author_facet Vitre, Benjamin
Gudimchuk, Nikita
Borda, Ranier
Kim, Yumi
Heuser, John E.
Cleveland, Don W.
Grishchuk, Ekaterina L.
author_sort Vitre, Benjamin
collection PubMed
description Centromere protein E (CENP-E) is a highly elongated kinesin that transports pole-proximal chromosomes during congression in prometaphase. During metaphase, it facilitates kinetochore–microtubule end-on attachment required to achieve and maintain chromosome alignment. In vitro CENP-E can walk processively along microtubule tracks and follow both growing and shrinking microtubule plus ends. Neither the CENP-E–dependent transport along microtubules nor its tip-tracking activity requires the unusually long coiled-coil stalk of CENP-E. The biological role for the CENP-E stalk has now been identified through creation of “Bonsai” CENP-E with significantly shortened stalk but wild-type motor and tail domains. We demonstrate that Bonsai CENP-E fails to bind microtubules in vitro unless a cargo is contemporaneously bound via its C-terminal tail. In contrast, both full-length and truncated CENP-E that has no stalk and tail exhibit robust motility with and without cargo binding, highlighting the importance of CENP-E stalk for its activity. Correspondingly, kinetochore attachment to microtubule ends is shown to be disrupted in cells whose CENP-E has a shortened stalk, thereby producing chromosome misalignment in metaphase and lagging chromosomes during anaphase. Together these findings establish an unexpected role of CENP-E elongated stalk in ensuring stability of kinetochore–microtubule attachments during chromosome congression and segregation.
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spelling pubmed-41163012014-10-16 Kinetochore–microtubule attachment throughout mitosis potentiated by the elongated stalk of the kinetochore kinesin CENP-E Vitre, Benjamin Gudimchuk, Nikita Borda, Ranier Kim, Yumi Heuser, John E. Cleveland, Don W. Grishchuk, Ekaterina L. Mol Biol Cell Articles Centromere protein E (CENP-E) is a highly elongated kinesin that transports pole-proximal chromosomes during congression in prometaphase. During metaphase, it facilitates kinetochore–microtubule end-on attachment required to achieve and maintain chromosome alignment. In vitro CENP-E can walk processively along microtubule tracks and follow both growing and shrinking microtubule plus ends. Neither the CENP-E–dependent transport along microtubules nor its tip-tracking activity requires the unusually long coiled-coil stalk of CENP-E. The biological role for the CENP-E stalk has now been identified through creation of “Bonsai” CENP-E with significantly shortened stalk but wild-type motor and tail domains. We demonstrate that Bonsai CENP-E fails to bind microtubules in vitro unless a cargo is contemporaneously bound via its C-terminal tail. In contrast, both full-length and truncated CENP-E that has no stalk and tail exhibit robust motility with and without cargo binding, highlighting the importance of CENP-E stalk for its activity. Correspondingly, kinetochore attachment to microtubule ends is shown to be disrupted in cells whose CENP-E has a shortened stalk, thereby producing chromosome misalignment in metaphase and lagging chromosomes during anaphase. Together these findings establish an unexpected role of CENP-E elongated stalk in ensuring stability of kinetochore–microtubule attachments during chromosome congression and segregation. The American Society for Cell Biology 2014-08-01 /pmc/articles/PMC4116301/ /pubmed/24920822 http://dx.doi.org/10.1091/mbc.E14-01-0698 Text en © 2014 Vitre, Gudimchuk, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Vitre, Benjamin
Gudimchuk, Nikita
Borda, Ranier
Kim, Yumi
Heuser, John E.
Cleveland, Don W.
Grishchuk, Ekaterina L.
Kinetochore–microtubule attachment throughout mitosis potentiated by the elongated stalk of the kinetochore kinesin CENP-E
title Kinetochore–microtubule attachment throughout mitosis potentiated by the elongated stalk of the kinetochore kinesin CENP-E
title_full Kinetochore–microtubule attachment throughout mitosis potentiated by the elongated stalk of the kinetochore kinesin CENP-E
title_fullStr Kinetochore–microtubule attachment throughout mitosis potentiated by the elongated stalk of the kinetochore kinesin CENP-E
title_full_unstemmed Kinetochore–microtubule attachment throughout mitosis potentiated by the elongated stalk of the kinetochore kinesin CENP-E
title_short Kinetochore–microtubule attachment throughout mitosis potentiated by the elongated stalk of the kinetochore kinesin CENP-E
title_sort kinetochore–microtubule attachment throughout mitosis potentiated by the elongated stalk of the kinetochore kinesin cenp-e
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116301/
https://www.ncbi.nlm.nih.gov/pubmed/24920822
http://dx.doi.org/10.1091/mbc.E14-01-0698
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