Intraflagellar transport motors in cilia: moving along the cell's antenna

Abstract

Intraflagellar transport (IFT), the motor-dependent movement of IFT particles along the axoneme, is critical for the assembly, maintenance, and function of motile and sensory cilia, and, consequently, this process underlies ciliary motility, cilium-based signaling, and ciliopathies. Here, I present my perspective on IFT as a model system for studying motor-driven cargo transport. I review evidence that kinesin-2 motors physically transport IFT particles as cargo and hypothesize that several accessory kinesins confer cilia-specific functions by augmenting the action of the two core IFT motors, kinesin-2 and dynein 1b, which assemble the cilium foundation.

Figure 1.

Pathways of IFT. (a) The canonical pathway of IFT. Heterotrimeric kinesin-2 moves IFT particles, ciliary precursors, and dynein 1b from the basal body to the distal tip of the cilium, where cargo unloading, motor switching, and turnaround occurs. Then, dynein 1b moves kinesin-2, turnover products, and IFT particles back to the cell body. This basic pathway is thought to build the core of the cilium in organisms such as Chlamydomonas and in C. elegans osm-3 mutants (Table I). (b) Anterograde transport pathways can be augmented by accessory kinesins. For example, in C. elegans sensory cilia, this produces sequential pathways of IFT. First, the concerted action of two members of the kinesin-2 family, kinesin-II and OSM-3, transports IFT particles along the middle segment of the axoneme in a process required to build the middle segment (corresponding to the cilium core). Second, OSM-3 alone then moves along the distal singlets, building and maintaining the distal segment as it goes. Finally, the kinesin-3 KLP-6 is required to target membrane proteins to the ciliary membrane, where they may be moved by KLP-6 itself and/or by other motors. Other accessory kinesins may target other ciliary components to the cilium, control ciliary length, or control ciliary motility, and the functional modulation of these motors may contribute to ciliary diversity.