Intraflagellar transport: from molecular characterisation to mechanism

Research from a wide range of model systems such as Chlamydomonas, C. elegans and mice have shown that intraflagellar transport (IFT) is a bidirectional motility of large protein complexes along cilia and flagella that is essential for building and maintaining these organelles. Since its discovery in 1993, much progress has been made in uncovering the molecular and functional basis of IFT. Presently, many components of the core IFT machinery are known, including the anterograde kinesin 2 motor(s), the IFT-dynein retrograde motor and the collection of at least 17 proteins that makes up the IFT particle. Most significantly, discoveries linking IFT to polycystic kidney disease and other developmental phenotypes have broadened the context of IFT research by demonstrating that primary cilia and IFT are required for processes such as kidney tubule and retinal tissue development, limb bud morphogenesis and organ patterning. Central to the functional basis of IFT is its ability to traffic various ciliary protein cargos, which include structural ciliary subunits, as well as non-structural proteins such as transmembrane channels/receptors and sensory signalling molecules. Indeed, exciting data over the past 3-4 years, linking IFT and primary cilia to developmental and growth factor signalling, as well as the cell cycle, indicates that the current repertoire of IFT cargos is likely to expand. Here we present a comprehensive review of IFT, with particular emphasis on its molecular composition and mechanism of action.