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Nat Cell Biol. 2015 Dec;17(12):1536-45. doi: 10.1038/ncb3263. Epub 2015 Nov 2.

Functional differentiation of cooperating kinesin-2 motors orchestrates cargo import and transport in C. elegans cilia.

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Department of Physics and Astronomy and LaserLaB Amsterdam, VU University Amsterdam, De Boelelaan 1081 1081 HV Amsterdam, The Netherlands.
Department of Molecular and Cellular Biology, University of California at Davis, Davis, California 95616, USA.


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.

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