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Curr Biol. 2019 Apr 22;29(8):1286-1300.e4. doi: 10.1016/j.cub.2019.02.062. Epub 2019 Apr 4.

A CCRK and a MAK Kinase Modulate Cilia Branching and Length via Regulation of Axonemal Microtubule Dynamics in Caenorhabditis elegans.

Author information

1
Department of Biology, Brandeis University, 415 South Street, Waltham, MA 02454, USA. Electronic address: ashishkm@brandeis.edu.
2
Department of Biology, Brandeis University, 415 South Street, Waltham, MA 02454, USA.
3
Department of Biology, Brandeis University, 415 South Street, Waltham, MA 02454, USA. Electronic address: sengupta@brandeis.edu.

Abstract

The diverse morphologies of primary cilia are tightly regulated as a function of cell type and cellular state. CCRK- and MAK-related kinases have been implicated in ciliary length control in multiple species, although the underlying mechanisms are not fully understood. Here, we show that in C. elegans, DYF-18/CCRK and DYF-5/MAK act in a cascade to generate the highly arborized cilia morphologies of the AWA olfactory neurons. Loss of kinase function results in dramatically elongated AWA cilia that lack branches. Intraflagellar transport (IFT) motor protein localization, but not velocities, in AWA cilia is altered upon loss of dyf-18. We instead find that axonemal microtubules are decorated by the EBP-2 end-binding protein along their lengths and that the tubulin load is increased and tubulin turnover is reduced in AWA cilia of dyf-18 mutants. Moreover, we show that predicted microtubule-destabilizing mutations in two tubulin subunits, as well as mutations in IFT proteins predicted to disrupt tubulin transport, restore cilia branching and suppress AWA cilia elongation in dyf-18 mutants. Loss of dyf-18 is also sufficient to elongate the truncated rod-like unbranched cilia of the ASH nociceptive neurons in animals carrying a microtubule-destabilizing mutation in a tubulin subunit. We suggest that CCRK and MAK activity tunes cilia length and shape in part via modulation of axonemal microtubule stability, suggesting that similar mechanisms may underlie their roles in ciliary length control in other cell types.

KEYWORDS:

AWA; C. elegans; CCRK; DYF-18; DYF-5; IFT; MAK; cilia; microtubules

PMID:
30955935
PMCID:
PMC6482063
[Available on 2020-04-22]
DOI:
10.1016/j.cub.2019.02.062

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