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MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons

Microtubule-dependent transport of vesicles and organelles appears saltatory because particles switch between periods of rest, random Brownian motion, and active transport. The transport can be regulated through motor proteins, cargo adaptors, or microtubule tracks. We report here a mechanism whereb...

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Autores principales: Mandelkow, Eva-Maria, Thies, Edda, Trinczek, Bernhard, Biernat, Jacek, Mandelkow, Eckard
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172520/
https://www.ncbi.nlm.nih.gov/pubmed/15466480
http://dx.doi.org/10.1083/jcb.200401085
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author Mandelkow, Eva-Maria
Thies, Edda
Trinczek, Bernhard
Biernat, Jacek
Mandelkow, Eckard
author_facet Mandelkow, Eva-Maria
Thies, Edda
Trinczek, Bernhard
Biernat, Jacek
Mandelkow, Eckard
author_sort Mandelkow, Eva-Maria
collection PubMed
description Microtubule-dependent transport of vesicles and organelles appears saltatory because particles switch between periods of rest, random Brownian motion, and active transport. The transport can be regulated through motor proteins, cargo adaptors, or microtubule tracks. We report here a mechanism whereby microtubule associated proteins (MAPs) represent obstacles to motors which can be regulated by microtubule affinity regulating kinase (MARK)/Par-1, a family of kinases that is known for its involvement in establishing cell polarity and in phosphorylating tau protein during Alzheimer neurodegeneration. Expression of MARK causes the phosphorylation of MAPs at their KXGS motifs, thereby detaching MAPs from the microtubules and thus facilitating the transport of particles. This occurs without impairing the intrinsic activity of motors because the velocity during active movement remains unchanged. In primary retinal ganglion cells, transfection with tau leads to the inhibition of axonal transport of mitochondria, APP vesicles, and other cell components which leads to starvation of axons and vulnerability against stress. This transport inhibition can be rescued by phosphorylating tau with MARK.
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spelling pubmed-21725202008-03-05 MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons Mandelkow, Eva-Maria Thies, Edda Trinczek, Bernhard Biernat, Jacek Mandelkow, Eckard J Cell Biol Research Articles Microtubule-dependent transport of vesicles and organelles appears saltatory because particles switch between periods of rest, random Brownian motion, and active transport. The transport can be regulated through motor proteins, cargo adaptors, or microtubule tracks. We report here a mechanism whereby microtubule associated proteins (MAPs) represent obstacles to motors which can be regulated by microtubule affinity regulating kinase (MARK)/Par-1, a family of kinases that is known for its involvement in establishing cell polarity and in phosphorylating tau protein during Alzheimer neurodegeneration. Expression of MARK causes the phosphorylation of MAPs at their KXGS motifs, thereby detaching MAPs from the microtubules and thus facilitating the transport of particles. This occurs without impairing the intrinsic activity of motors because the velocity during active movement remains unchanged. In primary retinal ganglion cells, transfection with tau leads to the inhibition of axonal transport of mitochondria, APP vesicles, and other cell components which leads to starvation of axons and vulnerability against stress. This transport inhibition can be rescued by phosphorylating tau with MARK. The Rockefeller University Press 2004-10-11 /pmc/articles/PMC2172520/ /pubmed/15466480 http://dx.doi.org/10.1083/jcb.200401085 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Mandelkow, Eva-Maria
Thies, Edda
Trinczek, Bernhard
Biernat, Jacek
Mandelkow, Eckard
MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons
title MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons
title_full MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons
title_fullStr MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons
title_full_unstemmed MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons
title_short MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons
title_sort mark/par1 kinase is a regulator of microtubule-dependent transport in axons
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172520/
https://www.ncbi.nlm.nih.gov/pubmed/15466480
http://dx.doi.org/10.1083/jcb.200401085
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