Cargando…

Regulation of microtubule-based transport by MAP4

Microtubule (MT)-based transport of organelles driven by the opposing MT motors kinesins and dynein is tightly regulated in cells, but the underlying molecular mechanisms remain largely unknown. Here we tested the regulation of MT transport by the ubiquitous protein MAP4 using Xenopus melanophores a...

Descripción completa

Detalles Bibliográficos
Autores principales: Semenova, Irina, Ikeda, Kazuho, Resaul, Karim, Kraikivski, Pavel, Aguiar, Mike, Gygi, Steven, Zaliapin, Ilya, Cowan, Ann, Rodionov, Vladimir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196864/
https://www.ncbi.nlm.nih.gov/pubmed/25143402
http://dx.doi.org/10.1091/mbc.E14-01-0022
_version_ 1782339536634773504
author Semenova, Irina
Ikeda, Kazuho
Resaul, Karim
Kraikivski, Pavel
Aguiar, Mike
Gygi, Steven
Zaliapin, Ilya
Cowan, Ann
Rodionov, Vladimir
author_facet Semenova, Irina
Ikeda, Kazuho
Resaul, Karim
Kraikivski, Pavel
Aguiar, Mike
Gygi, Steven
Zaliapin, Ilya
Cowan, Ann
Rodionov, Vladimir
author_sort Semenova, Irina
collection PubMed
description Microtubule (MT)-based transport of organelles driven by the opposing MT motors kinesins and dynein is tightly regulated in cells, but the underlying molecular mechanisms remain largely unknown. Here we tested the regulation of MT transport by the ubiquitous protein MAP4 using Xenopus melanophores as an experimental system. In these cells, pigment granules (melanosomes) move along MTs to the cell center (aggregation) or to the periphery (dispersion) by means of cytoplasmic dynein and kinesin-2, respectively. We found that aggregation signals induced phosphorylation of threonine residues in the MT-binding domain of the Xenopus MAP4 (XMAP4), thus decreasing binding of this protein to MTs. Overexpression of XMAP4 inhibited pigment aggregation by shortening dynein-dependent MT runs of melanosomes, whereas removal of XMAP4 from MTs reduced the length of kinesin-2–dependent runs and suppressed pigment dispersion. We hypothesize that binding of XMAP4 to MTs negatively regulates dynein-dependent movement of melanosomes and positively regulates kinesin-2–based movement. Phosphorylation during pigment aggregation reduces binding of XMAP4 to MTs, thus increasing dynein-dependent and decreasing kinesin-2–dependent motility of melanosomes, which stimulates their accumulation in the cell center, whereas dephosphorylation of XMAP4 during dispersion has an opposite effect.
format Online
Article
Text
id pubmed-4196864
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher The American Society for Cell Biology
record_format MEDLINE/PubMed
spelling pubmed-41968642014-12-30 Regulation of microtubule-based transport by MAP4 Semenova, Irina Ikeda, Kazuho Resaul, Karim Kraikivski, Pavel Aguiar, Mike Gygi, Steven Zaliapin, Ilya Cowan, Ann Rodionov, Vladimir Mol Biol Cell Articles Microtubule (MT)-based transport of organelles driven by the opposing MT motors kinesins and dynein is tightly regulated in cells, but the underlying molecular mechanisms remain largely unknown. Here we tested the regulation of MT transport by the ubiquitous protein MAP4 using Xenopus melanophores as an experimental system. In these cells, pigment granules (melanosomes) move along MTs to the cell center (aggregation) or to the periphery (dispersion) by means of cytoplasmic dynein and kinesin-2, respectively. We found that aggregation signals induced phosphorylation of threonine residues in the MT-binding domain of the Xenopus MAP4 (XMAP4), thus decreasing binding of this protein to MTs. Overexpression of XMAP4 inhibited pigment aggregation by shortening dynein-dependent MT runs of melanosomes, whereas removal of XMAP4 from MTs reduced the length of kinesin-2–dependent runs and suppressed pigment dispersion. We hypothesize that binding of XMAP4 to MTs negatively regulates dynein-dependent movement of melanosomes and positively regulates kinesin-2–based movement. Phosphorylation during pigment aggregation reduces binding of XMAP4 to MTs, thus increasing dynein-dependent and decreasing kinesin-2–dependent motility of melanosomes, which stimulates their accumulation in the cell center, whereas dephosphorylation of XMAP4 during dispersion has an opposite effect. The American Society for Cell Biology 2014-10-15 /pmc/articles/PMC4196864/ /pubmed/25143402 http://dx.doi.org/10.1091/mbc.E14-01-0022 Text en © 2014 Semenova et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Semenova, Irina
Ikeda, Kazuho
Resaul, Karim
Kraikivski, Pavel
Aguiar, Mike
Gygi, Steven
Zaliapin, Ilya
Cowan, Ann
Rodionov, Vladimir
Regulation of microtubule-based transport by MAP4
title Regulation of microtubule-based transport by MAP4
title_full Regulation of microtubule-based transport by MAP4
title_fullStr Regulation of microtubule-based transport by MAP4
title_full_unstemmed Regulation of microtubule-based transport by MAP4
title_short Regulation of microtubule-based transport by MAP4
title_sort regulation of microtubule-based transport by map4
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196864/
https://www.ncbi.nlm.nih.gov/pubmed/25143402
http://dx.doi.org/10.1091/mbc.E14-01-0022
work_keys_str_mv AT semenovairina regulationofmicrotubulebasedtransportbymap4
AT ikedakazuho regulationofmicrotubulebasedtransportbymap4
AT resaulkarim regulationofmicrotubulebasedtransportbymap4
AT kraikivskipavel regulationofmicrotubulebasedtransportbymap4
AT aguiarmike regulationofmicrotubulebasedtransportbymap4
AT gygisteven regulationofmicrotubulebasedtransportbymap4
AT zaliapinilya regulationofmicrotubulebasedtransportbymap4
AT cowanann regulationofmicrotubulebasedtransportbymap4
AT rodionovvladimir regulationofmicrotubulebasedtransportbymap4