title: Regulation of microtubule-based transport by MAP4.
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.
authors.affiliation: R.D. Berlin Center for Cell Analysis and Modeling and Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Irina
authors.initials: I
authors.lastname: Semenova
authors.affiliation: R.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.
authors.forename: Kazuho
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: R.D. Berlin Center for Cell Analysis and Modeling and Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Karim
authors.initials: K
authors.lastname: Resaul
authors.affiliation: R.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.
authors.forename: Pavel
authors.initials: P
authors.lastname: Kraikivski
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
authors.forename: Mike
authors.initials: M
authors.lastname: Aguiar
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115.
authors.forename: Steven
authors.initials: S
authors.lastname: Gygi
authors.affiliation: Department of Mathematics and Statistics, University of Nevada-Reno, Reno, NV 89557.
authors.forename: Ilya
authors.initials: I
authors.lastname: Zaliapin
authors.affiliation: R.D. Berlin Center for Cell Analysis and Modeling and Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030.
authors.forename: Ann
authors.initials: A
authors.lastname: Cowan
authors.affiliation: R.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.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Rodionov
mesh_terms: D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D004398:Dyneins / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism; D008547:Melanophores / Q000378:metabolism; D020460:Melanosomes / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D010766:Phosphorylation; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; D029867:Xenopus Proteins; D004398:Dyneins; D016547:Kinesins