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

• Published in: EMBO reports Vol. 18; no. 11; pp. 1947 - 1956
• Main Authors: Stepp, Willi L, Merck, Georg, Mueller‐Planitz, Felix, Ökten, Zeynep
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-11-2017; Blackwell Publishing Ltd; John Wiley and Sons Inc
• Subjects: Amphibian Proteins - chemistry; Amphibian Proteins - genetics; Amphibian Proteins - metabolism; Animals; Axonal transport; Axoneme - metabolism; Axoneme - ultrastructure; Axonemes; Baculoviridae - genetics; Baculoviridae - metabolism; Biological Transport; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Cilia - metabolism; Cilia - ultrastructure; Cloning, Molecular; Cytoplasm; EMBO05; EMBO20; Eukaryotes; Gene Expression; Genetic Vectors - chemistry; Genetic Vectors - metabolism; Helminth Proteins - chemistry; Helminth Proteins - genetics; Helminth Proteins - metabolism; heterodimeric kinesin‐2; intraflagellar transport; Kinesin; Kinesin - chemistry; Kinesin - genetics; Kinesin - metabolism; Machinery and equipment; Microtubules; Microtubules - metabolism; Microtubules - ultrastructure; Motors; Railroads; Railway tracks; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Scientific Report; Scientific Reports; Sf9 Cells; Spodoptera - cytology; Tracks (paths); Trains; Transport processes; Tubules; Walking; Xenopus laevis - genetics; Xenopus laevis - metabolism; heterodimeric kinesin‐2; axonemes; microtubules; intraflagellar transport
• ISSN: 1469-221X; 1469-3178
• DOI: 10.15252/embr.201744097

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.
Synopsis
The heterodimeric kinesin‐2 motor differentiates between microtubules and axonemes to move forward. This study suggests that step adaptation prevents head‐on collisions of large intraflagellar trains moving in opposite directions in the cilium.
The C‐terminal distal tail of heterodimeric kinesin‐2 asymmetrically impacts motor processivity.
Kinesin‐2 differently utilizes the microtubule and axoneme lattice for processive stepping.
The side‐stepping capability of kinesin‐2 offers an explanation for the two‐way traffic of intraflagellar transport trains on one doublet microtubule.
Graphical Abstract
The heterodimeric kinesin‐2 motor differentiates between microtubules and axonemes to move forward. This study suggests that step adaptation prevents head‐on collisions of large intraflagellar trains moving in opposite directions in the cilium.