AI Article Synopsis
- Microtubules help in separating chromosomes by connecting to kinetochores, but the process of stabilizing these connections is not fully understood.
- Using Astrin, a protein associated with kinetochores and microtubules, researchers found that the delivery of a protein called PP1 near a specific part of another protein (Ndc80) helps stabilize these connections rapidly.
- Disrupting this Astrin-PP1 delivery affects the stability of the connections and ultimately hinders proper chromosome movement, indicating that this system plays a crucial role in ensuring accurate chromosome segregation during cell division.
Article Abstract
Microtubules segregate chromosomes by attaching to macromolecular kinetochores. Only microtubule-end attached kinetochores can be pulled apart; how these end-on attachments are selectively recognised and stabilised is not known. Using the kinetochore and microtubule-associated protein, Astrin, as a molecular probe, we show that end-on attachments are rapidly stabilised by spatially-restricted delivery of PP1 near the C-terminus of Ndc80, a core kinetochore-microtubule linker. PP1 is delivered by the evolutionarily conserved tail of Astrin and this promotes Astrin's own enrichment creating a highly-responsive positive feedback, independent of biorientation. Abrogating Astrin:PP1-delivery disrupts attachment stability, which is not rescued by inhibiting Aurora-B, an attachment destabiliser, but is reversed by artificially tethering PP1 near the C-terminus of Ndc80. Constitutive Astrin:PP1-delivery disrupts chromosome congression and segregation, revealing a dynamic mechanism for stabilising attachments. Thus, Astrin-PP1 mediates a dynamic 'lock' that selectively and rapidly stabilises end-on attachments, independent of biorientation, and ensures proper chromosome segregation.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930079 | PMC |
| http://dx.doi.org/10.7554/eLife.49325 | DOI Listing |
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