Kinesin-2 motors adapt their stepping behavior for processive transport on axonemes and microtubules

EMBO Rep. 2017 Nov;18(11):1947-1956. doi: 10.15252/embr.201744097. Epub 2017 Sep 8.

Abstract

Two structurally distinct filamentous tracks, namely singlet microtubules in the cytoplasm and axonemes in the cilium, serve as railroads for long-range transport processes in vivo In all organisms studied so far, the kinesin-2 family is essential for long-range transport on axonemes. Intriguingly, in higher eukaryotes, kinesin-2 has been adapted to work on microtubules in the cytoplasm as well. Here, we show that heterodimeric kinesin-2 motors distinguish between axonemes and microtubules. Unlike canonical kinesin-1, kinesin-2 takes directional, off-axis steps on microtubules, but it resumes a straight path when walking on the axonemes. The inherent ability of kinesin-2 to side-track on the microtubule lattice restricts the motor to one side of the doublet microtubule in axonemes. The mechanistic features revealed here provide a molecular explanation for the previously observed partitioning of oppositely moving intraflagellar transport trains to the A- and B-tubules of the same doublet microtubule. Our results offer first mechanistic insights into why nature may have co-evolved the heterodimeric kinesin-2 with the ciliary machinery to work on the specialized axonemal surface for two-way traffic.

Keywords: axonemes; heterodimeric kinesin‐2; intraflagellar transport; microtubules.

MeSH terms

  • Amphibian Proteins / chemistry*
  • Amphibian Proteins / genetics
  • Amphibian Proteins / metabolism
  • Animals
  • Axoneme / metabolism*
  • Axoneme / ultrastructure
  • Baculoviridae / genetics
  • Baculoviridae / metabolism
  • Biological Transport
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Cilia / metabolism*
  • Cilia / ultrastructure
  • Cloning, Molecular
  • Gene Expression
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Helminth Proteins / chemistry*
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism
  • Kinesins / chemistry*
  • Kinesins / genetics
  • Kinesins / metabolism
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sf9 Cells
  • Spodoptera / cytology
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism

Substances

  • Amphibian Proteins
  • Helminth Proteins
  • Recombinant Proteins
  • Kinesins