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Kinetochores attached to microtubule-ends are stabilised by Astrin bound PP1 to ensure proper chromosome segregation.
Conti, Duccio; Gul, Parveen; Islam, Asifa; Martín-Durán, José M; Pickersgill, Richard W; Draviam, Viji M.
Afiliação
  • Conti D; School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom.
  • Gul P; Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
  • Islam A; School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom.
  • Martín-Durán JM; School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom.
  • Pickersgill RW; School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom.
  • Draviam VM; School of Biological and Chemical Sciences, Queen Mary University of London, London, United Kingdom.
Elife ; 82019 12 06.
Article em En | MEDLINE | ID: mdl-31808746
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenazinas / Fenotiazinas / Resorcinóis / Receptores de Neuropeptídeo Y / Cinetocoros / Segregação de Cromossomos / Azul Alciano / Microtúbulos Limite: Humans Idioma: En Revista: Elife Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fenazinas / Fenotiazinas / Resorcinóis / Receptores de Neuropeptídeo Y / Cinetocoros / Segregação de Cromossomos / Azul Alciano / Microtúbulos Limite: Humans Idioma: En Revista: Elife Ano de publicação: 2019 Tipo de documento: Article