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Mol Biol Cell. 2014 Oct 15;25(20):3119-32. doi: 10.1091/mbc.E14-01-0022. Epub 2014 Aug 20.

Regulation of microtubule-based transport by MAP4.

Author information

  • 1R.D. Berlin Center for Cell Analysis and Modeling and Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030.
  • 2R.D. Berlin Center for Cell Analysis and Modeling and Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030 Quantitative Biology Center, RIKEN, Osaka 565-0874, Japan.
  • 3R.D. Berlin Center for Cell Analysis and Modeling and Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030 Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061.
  • 4Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
  • 5Department of Mathematics and Statistics, University of Nevada-Reno, Reno, NV 89557.
  • 6R.D. Berlin Center for Cell Analysis and Modeling and Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030 rodionov@nso.uchc.edu.

Abstract

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.

PMID:
25143402
PMCID:
PMC4196864
DOI:
10.1091/mbc.E14-01-0022
[PubMed - indexed for MEDLINE]
Free PMC Article
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