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About the Authors:
Joost R. Broekhuis
Affiliation: Department of Cell Biology, Erasmus MC, Rotterdam, the Netherlands
Kristen J. Verhey
Affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America
Gert Jansen
* E-mail: [email protected]
Affiliation: Department of Cell Biology, Erasmus MC, Rotterdam, the Netherlands
Introduction
Primary cilia are microtubule-based protrusions that can be found on the surface of almost all vertebrate cells, and function as sensory organelles. Defects in cilia function, structure or length have been associated with many genetic diseases, collectively called ciliopathies [1]. The assembly and maintenance of primary cilia depends on intraflagellar transport (IFT), a microtubule-based transport system that involves kinesin motor proteins (kinesin-II and KIF17/OSM-3) which mediate anterograde transport (to the tip of the cilium), dynein motor complexes (cytoplasmic dynein 2), which mediate retrograde transport (back to the cell body), and adaptor complexes (complex A, complex B, and the BBSome) [2].
A wide variety in cilia lengths and morphologies exist, most likely to better support cilium function in specific tissues [3], [4]. Although several signaling molecules have been shown to modulate cilium length [5]–[7], how this is achieved mechanistically is not understood. The most plausible explanation is provided by the balance point model, in which cilium length is determined by a balance between cilium assembly and disassembly rates [8], [9]. The assembly rate is dependent on the availability of axonemal tubulin and other structural components, supplemented by anterograde IFT and probably the pool of these proteins at the base of the cilium [10], [11]. Indeed, changes in both anterograde and retrograde IFT are accompanied by changes in cilium length [8], [12]–[15]. How cilium disassembly is regulated is unclear, since it seems independent of retrograde IFT [8], [15].
The family of ros cross-hybridizing kinases (RCKs) is characterized by a MAP kinase-like Thr-Xaa-Tyr (TXY) motif in their activation loop, and an overall structure similar to CDKs [16], [17]. In Chlamydomonas (lf4), Leishmania (LmxMPK9), C. elegans (dyf-5), and mouse (Mak and Ick) RCKs have been identified that negatively regulate cilium length [12], [18]–[23]. Emerging evidence suggests that regulation of cilium length may be manifest by RCK-induced changes in IFT. In C. elegans, dyf-5 loss-of-function abolishes the...