CYK4 promotes antiparallel microtubule bundling by optimizing MKLP1 neck conformation.

Centralspindlin, a constitutive 2:2 heterotetramer of MKLP1 (a kinesin-6) and the non-motor subunit CYK4, plays important roles in cytokinesis. It is crucial for the formation of central spindle microtubule bundle structure. Its accumulation at the central antiparallel overlap zone is key for recrui...

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Main Authors: Tim Davies, Noriyuki Kodera, Gabriele S Kaminski Schierle, Eric Rees, Miklos Erdelyi, Clemens F Kaminski, Toshio Ando, Masanori Mishima
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-04-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.1002121
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author Tim Davies
Noriyuki Kodera
Gabriele S Kaminski Schierle
Eric Rees
Miklos Erdelyi
Clemens F Kaminski
Toshio Ando
Masanori Mishima
author_facet Tim Davies
Noriyuki Kodera
Gabriele S Kaminski Schierle
Eric Rees
Miklos Erdelyi
Clemens F Kaminski
Toshio Ando
Masanori Mishima
author_sort Tim Davies
collection DOAJ
description Centralspindlin, a constitutive 2:2 heterotetramer of MKLP1 (a kinesin-6) and the non-motor subunit CYK4, plays important roles in cytokinesis. It is crucial for the formation of central spindle microtubule bundle structure. Its accumulation at the central antiparallel overlap zone is key for recruitment and regulation of downstream cytokinesis factors and for stable anchoring of the plasma membrane at the midbody. Both MKLP1 and CYK4 are required for efficient microtubule bundling. However, the mechanism by which CYK4 contributes to this is unclear. Here we performed structural and functional analyses of centralspindlin using high-speed atomic force microscopy, Fӧrster resonance energy transfer analysis, and in vitro reconstitution. Our data reveal that CYK4 binds to a globular mass in the atypically long MKLP1 neck domain between the catalytic core and the coiled coil and thereby reconfigures the two motor domains in the MKLP1 dimer to be suitable for antiparallel microtubule bundling. Our work provides insights into the microtubule bundling during cytokinesis and into the working mechanisms of the kinesins with non-canonical neck structures.
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institution Kabale University
issn 1544-9173
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language English
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publisher Public Library of Science (PLoS)
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spelling doaj-art-2a18183aca604b2cb4f192f662639bd12025-08-20T03:46:42ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852015-04-01134e100212110.1371/journal.pbio.1002121CYK4 promotes antiparallel microtubule bundling by optimizing MKLP1 neck conformation.Tim DaviesNoriyuki KoderaGabriele S Kaminski SchierleEric ReesMiklos ErdelyiClemens F KaminskiToshio AndoMasanori MishimaCentralspindlin, a constitutive 2:2 heterotetramer of MKLP1 (a kinesin-6) and the non-motor subunit CYK4, plays important roles in cytokinesis. It is crucial for the formation of central spindle microtubule bundle structure. Its accumulation at the central antiparallel overlap zone is key for recruitment and regulation of downstream cytokinesis factors and for stable anchoring of the plasma membrane at the midbody. Both MKLP1 and CYK4 are required for efficient microtubule bundling. However, the mechanism by which CYK4 contributes to this is unclear. Here we performed structural and functional analyses of centralspindlin using high-speed atomic force microscopy, Fӧrster resonance energy transfer analysis, and in vitro reconstitution. Our data reveal that CYK4 binds to a globular mass in the atypically long MKLP1 neck domain between the catalytic core and the coiled coil and thereby reconfigures the two motor domains in the MKLP1 dimer to be suitable for antiparallel microtubule bundling. Our work provides insights into the microtubule bundling during cytokinesis and into the working mechanisms of the kinesins with non-canonical neck structures.https://doi.org/10.1371/journal.pbio.1002121
spellingShingle Tim Davies
Noriyuki Kodera
Gabriele S Kaminski Schierle
Eric Rees
Miklos Erdelyi
Clemens F Kaminski
Toshio Ando
Masanori Mishima
CYK4 promotes antiparallel microtubule bundling by optimizing MKLP1 neck conformation.
PLoS Biology
title CYK4 promotes antiparallel microtubule bundling by optimizing MKLP1 neck conformation.
title_full CYK4 promotes antiparallel microtubule bundling by optimizing MKLP1 neck conformation.
title_fullStr CYK4 promotes antiparallel microtubule bundling by optimizing MKLP1 neck conformation.
title_full_unstemmed CYK4 promotes antiparallel microtubule bundling by optimizing MKLP1 neck conformation.
title_short CYK4 promotes antiparallel microtubule bundling by optimizing MKLP1 neck conformation.
title_sort cyk4 promotes antiparallel microtubule bundling by optimizing mklp1 neck conformation
url https://doi.org/10.1371/journal.pbio.1002121
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