title: Kinetochore kinesin CENP-E is a processive bi-directional tracker of dynamic microtubule tips.
abstract: During vertebrate mitosis, the centromere-associated kinesin CENP-E (centromere protein E) transports misaligned chromosomes to the plus ends of spindle microtubules. Subsequently, the kinetochores that form at the centromeres establish stable associations with microtubule ends, which assemble and disassemble dynamically. Here we provide evidence that after chromosomes have congressed and bi-oriented, the CENP-E motor continues to play an active role at kinetochores, enhancing their links with dynamic microtubule ends. Using a combination of single-molecule approaches and laser trapping in vitro, we demonstrate that once reaching microtubule ends, CENP-E converts from a lateral transporter into a microtubule tip-tracker that maintains association with both assembling and disassembling microtubule tips. Computational modelling of this behaviour supports our proposal that CENP-E tip-tracks bi-directionally through a tethered motor mechanism, which relies on both the motor and tail domains of CENP-E. Our results provide a molecular framework for the contribution of CENP-E to the stability of attachments between kinetochores and dynamic microtubule ends.
authors: Physiology Department, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
authors: Nikita
authors: N
authors: Gudimchuk
authors: Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, Univ. of California, San Diego, La Jolla, CA, United States.
authors: Benjamin
authors: B
authors: Vitre
authors: Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, Univ. of California, San Diego, La Jolla, CA, United States.
authors: Yumi
authors: Y
authors: Kim
authors: Physiology Department, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
authors: Anatoly
authors: A
authors: Kiyatkin
authors: Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, Univ. of California, San Diego, La Jolla, CA, United States.
authors: Don W
authors: DW
authors: Cleveland
authors: Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russian Federation.|Federal Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation.
authors: Fazly I
authors: FI
authors: Ataullakhanov
authors: Physiology Department, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
authors: Ekaterina L
authors: EL
authors: Grishchuk
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism* / Q000648:ultrastructure; D040542:Mechanotransduction, Cellular / Q000235:genetics; D008870:Microtubules / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008938:Mitosis / Q000235:genetics*; D021381:Protein Transport; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C068688:centromere protein E
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