title: Functional differentiation of cooperating kinesin-2 motors orchestrates cargo import and transport in C. elegans cilia.
abstract: Intracellular transport depends on cooperation between distinct motor proteins. Two anterograde intraflagellar transport (IFT) motors, heterotrimeric kinesin-II and homodimeric OSM-3, cooperate to move cargo along Caenorhabditis elegans cilia. Here, using quantitative fluorescence microscopy, with single-molecule sensitivity, of IFT in living strains containing single-copy transgenes encoding fluorescent IFT proteins, we show that kinesin-II transports IFT trains through the ciliary base and transition zone to a 'handover zone' on the proximal axoneme. There, OSM-3 gradually replaces kinesin-II, yielding velocity profiles inconsistent with in vitro motility assays, and then drives transport to the ciliary tip. Dissociated kinesin-II motors undergo rapid turnaround and recycling to the ciliary base, whereas OSM-3 is recycled mainly to the handover zone. This reveals a functional differentiation in which the slower, less processive kinesin-II imports IFT trains into the cilium and OSM-3 drives their long-range transport, thereby optimizing cargo delivery.
authors.affiliation: Department of Physics and Astronomy and LaserLaB Amsterdam, VU University Amsterdam, De Boelelaan 1081 1081 HV Amsterdam, The Netherlands.
authors.forename: Bram
authors.initials: B
authors.lastname: Prevo
authors.affiliation: Department of Physics and Astronomy and LaserLaB Amsterdam, VU University Amsterdam, De Boelelaan 1081 1081 HV Amsterdam, The Netherlands.
authors.forename: Pierre
authors.initials: P
authors.lastname: Mangeol
authors.affiliation: Department of Physics and Astronomy and LaserLaB Amsterdam, VU University Amsterdam, De Boelelaan 1081 1081 HV Amsterdam, The Netherlands.
authors.forename: Felix
authors.initials: F
authors.lastname: Oswald
authors.affiliation: Department of Molecular and Cellular Biology, University of California at Davis, Davis, California 95616, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Scholey
authors.affiliation: Department of Physics and Astronomy and LaserLaB Amsterdam, VU University Amsterdam, De Boelelaan 1081 1081 HV Amsterdam, The Netherlands.
authors.forename: Erwin J G
authors.initials: EJ
authors.lastname: Peterman
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism; D000465:Algorithms; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D003198:Computer Simulation; D016547:Kinesins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009154:Mutation; D055503:Protein Multimerization; D014741:Video Recording
chemical_list: D054758:A Kinase Anchor Proteins; C112944:A kinase anchor protein (kap-1), C elegans; D029742:Caenorhabditis elegans Proteins; D008164:Luminescent Proteins; C093002:OSM-3 protein, C elegans; C074152:kinesin-II; D016547:Kinesins