title: Local inhibition of microtubule dynamics by dynein is required for neuronal cargo distribution.
abstract: Abnormal axonal transport is associated with neuronal disease. We identified a role for DHC-1, the C. elegans dynein heavy chain, in maintaining neuronal cargo distribution. Surprisingly, this does not involve dynein's role as a retrograde motor in cargo transport, hinging instead on its ability to inhibit microtubule (MT) dynamics. Neuronal MTs are highly static, yet the mechanisms and functional significance of this property are not well understood. In disease-mimicking dhc-1 alleles, excessive MT growth and collapse occur at the dendrite tip, resulting in the formation of aberrant MT loops. These unstable MTs act as cargo traps, leading to ectopic accumulations of cargo and reduced availability of cargo at normal locations. Our data suggest that an anchored dynein pool interacts with plus-end-out MTs to stabilize MTs and allow efficient retrograde transport. These results identify functional significance for neuronal MT stability and suggest a mechanism for cellular dysfunction in dynein-linked disease.
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, 385 Serra Mall, California 94305, USA.
authors.forename: Shaul
authors.initials: S
authors.lastname: Yogev
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, 385 Serra Mall, California 94305, USA.
authors.forename: Celine I
authors.initials: CI
authors.lastname: Maeder
authors.affiliation: Department of Electrical Engineering, Stanford University, 350 Serra Mall, California 94305, USA.
authors.forename: Roshni
authors.initials: R
authors.lastname: Cooper
authors.affiliation: Department of Electrical Engineering and Computer Science, Stanford University, 353 Serra Mall, California 94305, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Horowitz
authors.affiliation: Department of Bioengineering, McGill University, 817 Sherbrooke Street West, Montreal, Quebec, Canada H3A 0C3.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Hendricks
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, 385 Serra Mall, California 94305, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Shen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001370:Axonal Transport; D019556:COS Cells; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D056445:Cytoplasmic Dyneins / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism*; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D059008:Time-Lapse Imaging / Q000379:methods
chemical_list: D029742:Caenorhabditis elegans Proteins; D049452:Green Fluorescent Proteins; D056445:Cytoplasmic Dyneins; C502824:DHC-1 protein, C elegans