LF4/MOK and a CDK-related kinase regulate the number and length of cilia in Tetrahymena.
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
15
03
2019
accepted:
13
06
2019
revised:
05
08
2019
pubmed:
25
7
2019
medline:
18
12
2019
entrez:
25
7
2019
Statut:
epublish
Résumé
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. The multiciliated protist model, Tetrahymena, carries two types of cilia (oral and locomotory) and the length of the locomotory cilia is dependent on their position with the cell. In Tetrahymena, loss of an LF4/MOK ortholog, LF4A, lengthened the locomotory cilia, but also reduced their number. Without LF4A, cilia assembled faster and showed signs of increased intraflagellar transport (IFT). Consistently, overproduced LF4A shortened cilia and downregulated 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. We suggest that the distribution of LF4/MOK along the cilium delivers a uniform dose of inhibition to IFT trains that travel from the base to the tip. In a longer cilium, the IFT machinery may experience a higher cumulative dose of inhibition by LF4/MOK. Thus, LF4/MOK activity could be a readout of cilium length that helps to balance the rate of IFT-driven assembly with the rate of disassembly at steady state. We used a forward genetic screen to identify a CDK-related kinase, CDKR1, whose loss-of-function suppressed the shortening of cilia caused by overexpression of LF4A, by reducing its kinase activity. 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. The new genetic tools we developed here for Tetrahymena have potential for further dissection of the principles of cilia length regulation in multiciliated cells.
Identifiants
pubmed: 31339880
doi: 10.1371/journal.pgen.1008099
pii: PGENETICS-D-19-00429
pmc: PMC6682161
doi:
Substances chimiques
Protozoan Proteins
0
Cyclin-Dependent Kinases
EC 2.7.11.22
Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008099Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM110413
Pays : United States
Organisme : NICHD NIH HHS
ID : R21 HD092809
Pays : United States
Organisme : NINDS NIH HHS
ID : F31 NS074841
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM114409
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared no competing interests exist.
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