Molecular requirements for the inter-subunit interaction and kinetochore recruitment of SKAP and Astrin

Alexandra Friese, Alex C. Faesen, Pim J. Huis, Josef Fischböck, Daniel Prumbaum, Arsen Petrovic, Stefan Raunser, Franz Herzog, Andrea Musacchio

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

Abstract

Accurate chromosome segregation during cell division is crucial for propagating life and protects from cellular transformation. The SKAP:Astrin heterodimer localizes to spindle microtubules and to mature microtubule-kinetochore attachments during mitosis. Depletion of either subunit disrupts spindle structure and destabilizes kinetochore-microtubule attachments. Here, we identify molecular requirements for the inter-subunit interaction of SKAP and Astrin, and discuss requirements for their kinetochore recruitment. We also identify and characterize a microtubule-binding domain in SKAP, distinct from the SXIP motif that mediates end binding (EB) protein binding and plus end tracking, and show that it stimulates the growth-rate of microtubules, possibly through a direct interaction with tubulin. Mutations targeting this microtubule-binding domain impair microtubule plus-end tracking but not kinetochore targeting, and recapitulate many effects observed during depletion of SKAP. Collectively, our studies represent the first thorough mechanistic analysis of SKAP and Astrin, and significantly advance our functional understanding of these important mitotic proteins.

OriginalspracheEnglisch
Aufsatznummer11407
Seiten (von - bis)11407
FachzeitschriftNature Communications
Jahrgang7
DOIs
PublikationsstatusVeröffentlicht - 20 Apr. 2016
Extern publiziertJa

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