The kinetoplastid kinetochore protein KKT4 is an unconventional microtubule tip–coupling protein

Author:

Llauró Aida1ORCID,Hayashi Hanako2,Bailey Megan E.1,Wilson Alex2,Ludzia Patryk2,Asbury Charles L.1ORCID,Akiyoshi Bungo2ORCID

Affiliation:

1. Department of Physiology and Biophysics, University of Washington, Seattle, WA

2. Department of Biochemistry, University of Oxford, Oxford, UK

Abstract

Kinetochores are multiprotein machines that drive chromosome segregation by maintaining persistent, load-bearing linkages between chromosomes and dynamic microtubule tips. Kinetochores in commonly studied eukaryotes bind microtubules through widely conserved components like the Ndc80 complex. However, in evolutionarily divergent kinetoplastid species such as Trypanosoma brucei, which causes sleeping sickness, the kinetochores assemble from a unique set of proteins lacking homology to any known microtubule-binding domains. Here, we show that the T. brucei kinetochore protein KKT4 binds directly to microtubules and maintains load-bearing attachments to both growing and shortening microtubule tips. The protein localizes both to kinetochores and to spindle microtubules in vivo, and its depletion causes defects in chromosome segregation. We define a microtubule-binding domain within KKT4 and identify several charged residues important for its microtubule-binding activity. Thus, despite its lack of significant similarity to other known microtubule-binding proteins, KKT4 has key functions required for driving chromosome segregation. We propose that it represents a primary element of the kinetochore–microtubule interface in kinetoplastids.

Funder

Sackler Scholars

Uehara Memorial Foundation

National Institutes of Health

David and Lucile Packard Foundation

Sir Henry Dale

Wellcome Trust

Royal Society

Wellcome-Beit Prize

EPA Cephalosporin Fund

European Molecular Biology Organization

John Fell Fund, University of Oxford

Publisher

Rockefeller University Press

Subject

Cell Biology

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