Literature DB >> 31808746

Kinetochores attached to microtubule-ends are stabilised by Astrin bound PP1 to ensure proper chromosome segregation.

Parveen Gul1, Asifa Islam1, Duccio Conti1,2, José M Martín-Durán1, Richard W Pickersgill1, Viji M Draviam1,2.   

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.
© 2019, Conti et al.

Entities:  

Keywords:  cell biology; chromosome; human; kinetochore; microtubule; mitosis

Mesh:

Substances:

Year:  2019        PMID: 31808746      PMCID: PMC6930079          DOI: 10.7554/eLife.49325

Source DB:  PubMed          Journal:  Elife        ISSN: 2050-084X            Impact factor:   8.140


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