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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11 October 2004
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October 04 2004
MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons
Eva-Maria Mandelkow,
Eva-Maria Mandelkow
Max-Planck Unit for Structural Molecular Biology, 22607 Hamburg, Germany
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Edda Thies,
Edda Thies
Max-Planck Unit for Structural Molecular Biology, 22607 Hamburg, Germany
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Bernhard Trinczek,
Bernhard Trinczek
Max-Planck Unit for Structural Molecular Biology, 22607 Hamburg, Germany
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Jacek Biernat,
Jacek Biernat
Max-Planck Unit for Structural Molecular Biology, 22607 Hamburg, Germany
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Eckard Mandelkow
Eckard Mandelkow
Max-Planck Unit for Structural Molecular Biology, 22607 Hamburg, Germany
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Eva-Maria Mandelkow
Max-Planck Unit for Structural Molecular Biology, 22607 Hamburg, Germany
Edda Thies
Max-Planck Unit for Structural Molecular Biology, 22607 Hamburg, Germany
Bernhard Trinczek
Max-Planck Unit for Structural Molecular Biology, 22607 Hamburg, Germany
Jacek Biernat
Max-Planck Unit for Structural Molecular Biology, 22607 Hamburg, Germany
Eckard Mandelkow
Max-Planck Unit for Structural Molecular Biology, 22607 Hamburg, Germany
Correspondence to Eva Marie Mandelkow: [email protected]
B. Trinczek's present address is Dept. of Medicinal Chemistry, University of Kansas, Lawrence, KS 66045.
Abbreviations used in this paper: APP, amyloid precursor protein; MAP, microtubule associated protein; MARK, microtubule affinity regulating kinase; RGC, retinal ganglion cell.
Received:
January 16 2004
Accepted:
August 30 2004
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2004
J Cell Biol (2004) 167 (1): 99–110.
Article history
Received:
January 16 2004
Accepted:
August 30 2004
Citation
Eva-Maria Mandelkow, Edda Thies, Bernhard Trinczek, Jacek Biernat, Eckard Mandelkow; MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons . J Cell Biol 11 October 2004; 167 (1): 99–110. doi: https://doi.org/10.1083/jcb.200401085
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