title: Load-induced enhancement of Dynein force production by LIS1-NudE in vivo and in vitro.
abstract: Most sub-cellular cargos are transported along microtubules by kinesin and dynein molecular motors, but how transport is regulated is not well understood. It is unknown whether local control is possible, for example, by changes in specific cargo-associated motor behaviour to react to impediments. Here we discover that microtubule-associated lipid droplets (LDs) in COS1 cells respond to an optical trap with a remarkable enhancement in sustained force production. This effect is observed only for microtubule minus-end-moving LDs. It is specifically blocked by RNAi for the cytoplasmic dynein regulators LIS1 and NudE/L (Nde1/Ndel1), but not for the dynactin p150(Glued) subunit. It can be completely replicated using cell-free preparations of purified LDs, where duration of LD force production is more than doubled. These results identify a novel, intrinsic, cargo-associated mechanism for dynein-mediated force adaptation, which should markedly improve the ability of motor-driven cargoes to overcome subcellular obstacles.
authors.affiliation: Department of Developmental and Cell Biology, University of California Irvine, Irvine, California 92697, USA.
authors.forename: Babu J N
authors.initials: BJ
authors.lastname: Reddy
authors.affiliation: Department of Developmental and Cell Biology, University of California Irvine, Irvine, California 92697, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Mattson
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York 10032, USA.
authors.forename: Caitlin L
authors.initials: CL
authors.lastname: Wynne
authors.affiliation: Department of Developmental and Cell Biology, University of California Irvine, Irvine, California 92697, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Vadpey
authors.affiliation: Department of Developmental and Cell Biology, University of California Irvine, Irvine, California 92697, USA.
authors.forename: Abdo
authors.initials: A
authors.lastname: Durra
authors.affiliation: Department of Developmental and Cell Biology, University of California Irvine, Irvine, California 92697, USA.
authors.forename: Dail
authors.initials: D
authors.lastname: Chapman
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York 10032, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Vallee
authors.affiliation: Department of Developmental and Cell Biology, University of California Irvine, Irvine, California 92697, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gross
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004331:Drosophila melanogaster; D004398:Dyneins / Q000378:metabolism*; D066292:Lipid Droplets / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008954:Models, Biological; D009038:Motion
chemical_list: D002352:Carrier Proteins; D008869:Microtubule-Associated Proteins; D004398:Dyneins