Crossref journal-article
Rockefeller University Press
The Journal of Cell Biology (291)
Abstract

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.

Bibliography

Mandelkow, E.-M., Thies, E., Trinczek, B., Biernat, J., & Mandelkow, E. (2004). MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons. The Journal of Cell Biology, 167(1), 99–110.

Authors 5
  1. Eva-Maria Mandelkow (first)
  2. Edda Thies (additional)
  3. Bernhard Trinczek (additional)
  4. Jacek Biernat (additional)
  5. Eckard Mandelkow (additional)
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Dates
Type When
Created 20 years, 11 months ago (Oct. 4, 2004, 8:13 p.m.)
Deposited 1 year, 7 months ago (Jan. 14, 2024, 9:14 a.m.)
Indexed 2 days, 21 hours ago (Sept. 3, 2025, 6:25 a.m.)
Issued 20 years, 11 months ago (Oct. 4, 2004)
Published 20 years, 11 months ago (Oct. 4, 2004)
Published Online 20 years, 11 months ago (Oct. 4, 2004)
Published Print 20 years, 10 months ago (Oct. 11, 2004)
Funders 0

None

@article{Mandelkow_2004, title={MARK/PAR1 kinase is a regulator of microtubule-dependent transport in axons}, volume={167}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200401085}, DOI={10.1083/jcb.200401085}, number={1}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Mandelkow, Eva-Maria and Thies, Edda and Trinczek, Bernhard and Biernat, Jacek and Mandelkow, Eckard}, year={2004}, month=oct, pages={99–110} }