LF4/MOK and a CDK-related kinase regulate the number and length of cilia in Tetrahymena
Krishna Kumar Vasudevan,
Karl F Lechtreck,
Posted 19 Mar 2019
bioRxiv DOI: 10.1101/582833 (published DOI: 10.1371/journal.pgen.1008099)
Posted 19 Mar 2019
The length of cilia is controlled by a poorly understood mechanism that involves members of the conserved RCK kinase group, and among them, the LF4/MOK kinases. In Tetrahymena, a loss of an LF4/MOK ortholog, LF4A, lengthened the locomotory cilia, but also reduced their total number per cell. Without LF4A, cilia assembled faster and showed signs of increased intraflagellar transport (IFT). Consistently, overproduced LF4A shortened cilia and downregulated the IFT. GFP-tagged LF4A, expressed in the native locus and imaged by total internal reflection microscopy, was enriched at the basal bodies and distributed along the shafts of cilia. Within cilia, most LF4A-GFP particles were immobile and a few either diffused or moved by IFT. A forward genetic screen identified a CDK-related kinase, CDKR1, whose loss-of-function suppressed the shortening of cilia caused by overexpression of LF4A, by reducing its kinase activity. A loss of CDKR1 alone lengthened both the locomotory and oral cilia. CDKR1 resembles other known ciliary CDK-related kinases: LF2 of Chlamydomonas, mammalian CCRK and DYF-18 of C. elegans, in lacking the cyclin-binding motif and acting upstream of RCKs. We propose that the total LF4/MOK activity per cilium is dependent on both its activation by an upstream CDK-related kinase and cilium length. Previous studies showed that the rate of assembly is high in growing cilia and decreases as cilia elongate to achieve the steady-state length. We propose that in a longer cilium, the IFT components, which travel from the base to the tip, are subjected to a higher dose of inhibition by the uniformly distributed LF4/MOK. Thus, in a feedback loop, LF4/MOK may translate cilium length into proportional inhibition of IFT, to balance the rates of assembly and disassembly at steady-state.
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