The kinetochore encodes a mechanical switch to disrupt spindle assembly checkpoint signaling
The Spindle Assembly Checkpoint (SAC) is a unique signaling mechanism that responds to the state of attachment of the kinetochore to spindle microtubules. SAC signaling is activated by unattached kinetochores, and it is silenced after these kinetochores form end-on microtubule attachments. Although...
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2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630029/ |
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pubmed-4630029 |
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pubmed-46300292016-01-01 The kinetochore encodes a mechanical switch to disrupt spindle assembly checkpoint signaling Aravamudhan, Pavithra Goldfarb, Alan A. Joglekar, Ajit P. Article The Spindle Assembly Checkpoint (SAC) is a unique signaling mechanism that responds to the state of attachment of the kinetochore to spindle microtubules. SAC signaling is activated by unattached kinetochores, and it is silenced after these kinetochores form end-on microtubule attachments. Although the biochemical cascade of SAC signaling is well-understood, how kinetochore-microtubule attachment disrupts it remained unknown. Here we show that, in budding yeast, end-on microtubule attachment to the kinetochore physically separates the Mps1 kinase, which likely binds to the Calponin homology domain of Ndc80, from the kinetochore substrate of Mps1, Spc105 (KNL1 orthologue). This attachment-mediated separation disrupts the phosphorylation of Spc105, and enables SAC silencing. Additionally, the Dam1 complex may act as a barrier that shields Spc105 from Mps1. Together these data suggest that the protein architecture of the kinetochore encodes a mechanical switch. End-on microtubule attachment to the kinetochore turns this switch off to silence the SAC. 2015-06-08 2015-07 /pmc/articles/PMC4630029/ /pubmed/26053220 http://dx.doi.org/10.1038/ncb3179 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Aravamudhan, Pavithra Goldfarb, Alan A. Joglekar, Ajit P. |
| spellingShingle |
Aravamudhan, Pavithra Goldfarb, Alan A. Joglekar, Ajit P. The kinetochore encodes a mechanical switch to disrupt spindle assembly checkpoint signaling |
| author_facet |
Aravamudhan, Pavithra Goldfarb, Alan A. Joglekar, Ajit P. |
| author_sort |
Aravamudhan, Pavithra |
| title |
The kinetochore encodes a mechanical switch to disrupt spindle assembly checkpoint signaling |
| title_short |
The kinetochore encodes a mechanical switch to disrupt spindle assembly checkpoint signaling |
| title_full |
The kinetochore encodes a mechanical switch to disrupt spindle assembly checkpoint signaling |
| title_fullStr |
The kinetochore encodes a mechanical switch to disrupt spindle assembly checkpoint signaling |
| title_full_unstemmed |
The kinetochore encodes a mechanical switch to disrupt spindle assembly checkpoint signaling |
| title_sort |
kinetochore encodes a mechanical switch to disrupt spindle assembly checkpoint signaling |
| description |
The Spindle Assembly Checkpoint (SAC) is a unique signaling mechanism that responds to the state of attachment of the kinetochore to spindle microtubules. SAC signaling is activated by unattached kinetochores, and it is silenced after these kinetochores form end-on microtubule attachments. Although the biochemical cascade of SAC signaling is well-understood, how kinetochore-microtubule attachment disrupts it remained unknown. Here we show that, in budding yeast, end-on microtubule attachment to the kinetochore physically separates the Mps1 kinase, which likely binds to the Calponin homology domain of Ndc80, from the kinetochore substrate of Mps1, Spc105 (KNL1 orthologue). This attachment-mediated separation disrupts the phosphorylation of Spc105, and enables SAC silencing. Additionally, the Dam1 complex may act as a barrier that shields Spc105 from Mps1. Together these data suggest that the protein architecture of the kinetochore encodes a mechanical switch. End-on microtubule attachment to the kinetochore turns this switch off to silence the SAC. |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4630029/ |
| _version_ |
1613496244025425920 |