Intraflagellar transport velocity is governed by the number of active KIF17 and KIF3AB motors and their motility properties under load

Homodimeric KIF17 and heterotrimeric KIF3AB are processive, kinesin-2 family motors that act jointly to carry out anterograde intraflagellar transport (IFT), ferrying cargo along microtubules (MTs) toward the tips of cilia. How IFT trains attain speeds that exceed the unloaded rate of the slower, KI...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2017-08, Vol.114 (33), p.E6830-E6838
Main Authors: Milic, Bojan, Andreasson, Johan O. L., Hogan, Daniel W., Block, Steven M.
Format: Article
Language:English
Subjects:
Algorithms
Animals
Biological Sciences
Biological Transport
Biophysics
Cilia
Cilia - metabolism
Flagella - metabolism
Humans
Kinesin
Kinesin - chemistry
Kinesin - genetics
Kinesin - metabolism
Kinetics
Microtubules
Microtubules - metabolism
Motors
PNAS Plus
Protein Binding
Protein Multimerization
Recombinant Proteins - chemistry
Recombinant Proteins - metabolism
Sf9 Cells
Spodoptera
Tips
Transport
Velocity
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Summary:Homodimeric KIF17 and heterotrimeric KIF3AB are processive, kinesin-2 family motors that act jointly to carry out anterograde intraflagellar transport (IFT), ferrying cargo along microtubules (MTs) toward the tips of cilia. How IFT trains attain speeds that exceed the unloaded rate of the slower, KIF3AB motor remains unknown. By characterizing the motility properties of kinesin-2 motors as a function of load we find that the increase in KIF3AB velocity, elicited by forward loads from KIF17 motors, cannot alone account for the speed of IFT trains in vivo. Instead, higher IFT velocities arise from an increased likelihood that KIF3AB motors dissociate from the MT, resulting in transport by KIF17 motors alone, unencumbered by opposition from KIF3AB. The rate of transport is therefore set by an equilibrium between a faster state, where only KIF17 motors move the train, and a slower state, where at least one KIF3AB motor on the train remains active in transport. The more frequently the faster state is accessed, the higher the overall velocity of the IFT train. We conclude that IFT velocity is governed by (i) the absolute numbers of each motor type on a given train, (ii) how prone KIF3AB is to dissociation from MTs relative to KIF17, and (iii) how prone both motors are to dissociation relative to binding MTs.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1708157114