Intraflagellar transport: mechanisms of motor action, cooperation, and cargo delivery.
Intraflagellar transport (IFT) is a form of motor-dependent cargo transport that is essential for the assembly, maintenance, and length control of cilia, which play critical roles in motility, sensory reception, and signal transduction in virtually all eukaryotic cells. During IFT, anterograde kinesin-2 and retrograde IFT dynein motors drive the bidirectional transport of IFT trains that deliver cargo, for example, axoneme precursors such as tubulins as well as molecules of the signal transduction machinery, to their site of assembly within the cilium. Following its discovery in Chlamydomonas, IFT has emerged as a powerful model system for studying general principles of motor-dependent cargo transport and we now appreciate the diversity that exists in the mechanism of IFT within cilia of different cell types. The absence of heterotrimeric kinesin-2 function, for example, causes a complete loss of both IFT and cilia in Chlamydomonas, but following its loss in Caenorhabditis elegans, where its primary function is loading the IFT machinery into cilia, homodimeric kinesin-2-driven IFT persists and assembles a full-length cilium. Generally, heterotrimeric kinesin-2 and IFT dynein motors are thought to play widespread roles as core IFT motors, whereas homodimeric kinesin-2 motors are accessory motors that mediate different functions in a broad range of cilia, in some cases contributing to axoneme assembly or the delivery of signaling molecules but in many other cases their ciliary functions, if any, remain unknown. In this review, we focus on mechanisms of motor action, motor cooperation, and motor-dependent cargo delivery during IFT.
Department of Cellular & Molecular Medicine, University of California San Diego, CA, USA.|Ludwig Institute for Cancer Research, San Diego, CA, USA.
Bram
B
Prevo
Department of Molecular & Cell Biology, University of California Davis, CA, USA.
Jonathan M
JM
Scholey
Department of Physics and Astronomy and LaserLaB Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands.
Erwin J G
EJG
Peterman
D000818:Animals; D054468:Axoneme / Q000378:metabolism / Q000648:ultrastructure; D064652:Basal Bodies / Q000378:metabolism / Q000648:ultrastructure; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D002696:Chlamydomonas / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D002923:Cilia / Q000378:metabolism* / Q000648:ultrastructure; D004398:Dyneins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005407:Flagella / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D016547:Kinesins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D015398:Signal Transduction; D014404:Tubulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D014404:Tubulin; D004398:Dyneins; D016547:Kinesins
IFT dynein; intraflagellar transport; kinesin-2; motor cooperation