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Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK
BACKGROUND: Proper attachment of chromosomes to microtubules is crucial for the accurate segregation of chromosomes. Human chromosomes attach initially to lateral walls of microtubules. Subsequently, attachments to lateral walls disappear and attachments to microtubule ends (end-on attachments) pred...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748344/ https://www.ncbi.nlm.nih.gov/pubmed/23891108 http://dx.doi.org/10.1016/j.cub.2013.06.040 |
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author | Shrestha, Roshan L. Draviam, Viji M. |
author_facet | Shrestha, Roshan L. Draviam, Viji M. |
author_sort | Shrestha, Roshan L. |
collection | PubMed |
description | BACKGROUND: Proper attachment of chromosomes to microtubules is crucial for the accurate segregation of chromosomes. Human chromosomes attach initially to lateral walls of microtubules. Subsequently, attachments to lateral walls disappear and attachments to microtubule ends (end-on attachments) predominate. While it is known in yeasts that lateral to end-on conversion of attachments occurs through a multistep process, equivalent conversion steps in humans remain unknown. RESULTS: By developing a high-resolution imaging assay to visualize intermediary steps of the lateral to end-on conversion process, we show that the mechanisms that bring a laterally bound chromosome and its microtubule end closer to each other are indispensable for proper end-on attachment because laterally attached chromosomes seldom detach. We show that end-on conversion requires (1) the plus-end-directed motor CENP-E to tether the lateral kinetochore onto microtubule walls and (2) the microtubule depolymerizer MCAK to release laterally attached microtubules after a partial end-on attachment is formed. CONCLUSIONS: By uncovering a CENP-E mediated wall-tethering event and a MCAK-mediated wall-removing event, we establish that human chromosome-microtubule attachment is achieved through a set of deterministic sequential events rather than stochastic direct capture of microtubule ends. |
format | Online Article Text |
id | pubmed-3748344 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-37483442013-08-21 Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK Shrestha, Roshan L. Draviam, Viji M. Curr Biol Article BACKGROUND: Proper attachment of chromosomes to microtubules is crucial for the accurate segregation of chromosomes. Human chromosomes attach initially to lateral walls of microtubules. Subsequently, attachments to lateral walls disappear and attachments to microtubule ends (end-on attachments) predominate. While it is known in yeasts that lateral to end-on conversion of attachments occurs through a multistep process, equivalent conversion steps in humans remain unknown. RESULTS: By developing a high-resolution imaging assay to visualize intermediary steps of the lateral to end-on conversion process, we show that the mechanisms that bring a laterally bound chromosome and its microtubule end closer to each other are indispensable for proper end-on attachment because laterally attached chromosomes seldom detach. We show that end-on conversion requires (1) the plus-end-directed motor CENP-E to tether the lateral kinetochore onto microtubule walls and (2) the microtubule depolymerizer MCAK to release laterally attached microtubules after a partial end-on attachment is formed. CONCLUSIONS: By uncovering a CENP-E mediated wall-tethering event and a MCAK-mediated wall-removing event, we establish that human chromosome-microtubule attachment is achieved through a set of deterministic sequential events rather than stochastic direct capture of microtubule ends. Cell Press 2013-08-19 /pmc/articles/PMC3748344/ /pubmed/23891108 http://dx.doi.org/10.1016/j.cub.2013.06.040 Text en © 2013 The Authors https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license |
spellingShingle | Article Shrestha, Roshan L. Draviam, Viji M. Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK |
title | Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK |
title_full | Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK |
title_fullStr | Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK |
title_full_unstemmed | Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK |
title_short | Lateral to End-on Conversion of Chromosome-Microtubule Attachment Requires Kinesins CENP-E and MCAK |
title_sort | lateral to end-on conversion of chromosome-microtubule attachment requires kinesins cenp-e and mcak |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748344/ https://www.ncbi.nlm.nih.gov/pubmed/23891108 http://dx.doi.org/10.1016/j.cub.2013.06.040 |
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