Abstract

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.

Highlights

  • IntroductionCilia are microtubule (MT)-based organelles that protrude from the surface of virtually all eukaryotic cells [1]

  • Basic Mechanism and Functions of Intraflagellar transport (IFT)Cilia are microtubule (MT)-based organelles that protrude from the surface of virtually all eukaryotic cells [1]

  • The current view is that anterograde IFT trains, which deliver a variety of cargo molecules for incorporation into the ciliary axoneme, membrane and matrix, are moved from the base to the distal tip of the cilium by heterotrimeric and, in some cases, homodimeric motors of the kinesin-2 family, whereas retrograde IFT trains, which recycle turnover products from the tip to the base of the cilium are moved by IFT-dynein (Fig. 1B–D) [24, 25]

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Summary

Introduction

Cilia are microtubule (MT)-based organelles that protrude from the surface of virtually all eukaryotic cells [1]. The discovery of intraflagellar transport as a critical component of the mechanism of ciliogenesis was catalyzed by the observation that polystyrene beads could move along the motile cilia of Chlamydomonas in a bidirectional fashion, independent of ciliary beating [6, 7] This paved the way for a series of pioneering experiments which revealed that ciliary precursors that form in the cell body, e.g. tubulin subunits and pre-assembled motilityrelated complexes, assemble onto the distal tips of the 10 μm long, motile Chlamydomonas cilium [8]. IFT is thought to play key roles in cilium-based signaling, by building the foundation of the ciliary antenna, and by delivering signaling molecules as cargo to the ciliary membrane and matrix and it possibly plays a more direct, yet poorly understood role in the mechanism of signal transduction itself This topic has been nicely covered in several recent reviews e.g. This topic has been nicely covered in several recent reviews e.g. [39, 40]

Structure of Cilia and IFT trains
Biochemistry and Functions of components of the IFT Machinery
Mechanism of Action of IFT-motors
Motor Cooperation and Regulation during IFT
Cargo Delivery by IFT
IFT in different Model Systems
Concluding remarks
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