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Dynactin has two antagonistic regulatory domains and exerts opposing effects on dynein motility

Dynactin is a dynein-regulating protein that increases the processivity of dynein movement on microtubules. Recent studies have shown that a tripartite complex of dynein–dynactin–Bicaudal D2 is essential for highly processive movement. To elucidate the regulation of dynein motility by dynactin, we f...

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Autores principales: Kobayashi, Takuya, Miyashita, Takuya, Murayama, Takashi, Toyoshima, Yoko Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574551/
https://www.ncbi.nlm.nih.gov/pubmed/28850609
http://dx.doi.org/10.1371/journal.pone.0183672
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author Kobayashi, Takuya
Miyashita, Takuya
Murayama, Takashi
Toyoshima, Yoko Y.
author_facet Kobayashi, Takuya
Miyashita, Takuya
Murayama, Takashi
Toyoshima, Yoko Y.
author_sort Kobayashi, Takuya
collection PubMed
description Dynactin is a dynein-regulating protein that increases the processivity of dynein movement on microtubules. Recent studies have shown that a tripartite complex of dynein–dynactin–Bicaudal D2 is essential for highly processive movement. To elucidate the regulation of dynein motility by dynactin, we focused on two isoforms (A and B) of dynactin 1 (DCTN1), the largest subunit of dynactin that contains both microtubule- and dynein-binding domains. The only difference between the primary structures of the two isoforms is that DCTN1B lacks the K-rich domain, a cluster of basic residues. We measured dynein motility by single molecule observation of recombinant dynein and dynactin. Whereas the tripartite complex containing DCTN1A exhibited highly processive movement, the complex containing DCTN1B dissociated from microtubules with no apparent processive movement. This inhibitory effect of DCTN1B was caused by reductions of the microtubule-binding affinities of both dynein and dynactin, which was attributed to the coiled-coil 1 domain of DCTN1. In DCTN1A, the K-rich domain antagonized these inhibitory effects. Therefore, dynactin has two antagonistic domains and promotes or suppresses dynein motility to accomplish correct localization and functions of dynein within a cell.
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spelling pubmed-55745512017-09-15 Dynactin has two antagonistic regulatory domains and exerts opposing effects on dynein motility Kobayashi, Takuya Miyashita, Takuya Murayama, Takashi Toyoshima, Yoko Y. PLoS One Research Article Dynactin is a dynein-regulating protein that increases the processivity of dynein movement on microtubules. Recent studies have shown that a tripartite complex of dynein–dynactin–Bicaudal D2 is essential for highly processive movement. To elucidate the regulation of dynein motility by dynactin, we focused on two isoforms (A and B) of dynactin 1 (DCTN1), the largest subunit of dynactin that contains both microtubule- and dynein-binding domains. The only difference between the primary structures of the two isoforms is that DCTN1B lacks the K-rich domain, a cluster of basic residues. We measured dynein motility by single molecule observation of recombinant dynein and dynactin. Whereas the tripartite complex containing DCTN1A exhibited highly processive movement, the complex containing DCTN1B dissociated from microtubules with no apparent processive movement. This inhibitory effect of DCTN1B was caused by reductions of the microtubule-binding affinities of both dynein and dynactin, which was attributed to the coiled-coil 1 domain of DCTN1. In DCTN1A, the K-rich domain antagonized these inhibitory effects. Therefore, dynactin has two antagonistic domains and promotes or suppresses dynein motility to accomplish correct localization and functions of dynein within a cell. Public Library of Science 2017-08-29 /pmc/articles/PMC5574551/ /pubmed/28850609 http://dx.doi.org/10.1371/journal.pone.0183672 Text en © 2017 Kobayashi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kobayashi, Takuya
Miyashita, Takuya
Murayama, Takashi
Toyoshima, Yoko Y.
Dynactin has two antagonistic regulatory domains and exerts opposing effects on dynein motility
title Dynactin has two antagonistic regulatory domains and exerts opposing effects on dynein motility
title_full Dynactin has two antagonistic regulatory domains and exerts opposing effects on dynein motility
title_fullStr Dynactin has two antagonistic regulatory domains and exerts opposing effects on dynein motility
title_full_unstemmed Dynactin has two antagonistic regulatory domains and exerts opposing effects on dynein motility
title_short Dynactin has two antagonistic regulatory domains and exerts opposing effects on dynein motility
title_sort dynactin has two antagonistic regulatory domains and exerts opposing effects on dynein motility
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574551/
https://www.ncbi.nlm.nih.gov/pubmed/28850609
http://dx.doi.org/10.1371/journal.pone.0183672
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