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Publication : TTBK2 controls cilium stability by regulating distinct modules of centrosomal proteins.

First Author  Nguyen A Year  2023
Journal  Mol Biol Cell Volume  34
Issue  1 Pages  ar8
PubMed ID  36322399 Mgi Jnum  J:334496
Mgi Id  MGI:7441862 Doi  10.1091/mbc.E22-08-0373
Citation  Nguyen A, et al. (2023) TTBK2 controls cilium stability by regulating distinct modules of centrosomal proteins. Mol Biol Cell 34(1):ar8
abstractText  The serine-threonine kinase tau tubulin kinase 2 (TTBK2) is a key regulator of the assembly of primary cilia, which are vital signaling organelles. TTBK2 is also implicated in the stability of the assembled cilium through mechanisms that remain to be defined. Here we use mouse embryonic fibroblasts derived from Ttbk2(fl/fl), UBC-CreERT+ embryos (hereafter Ttbk2(cmut)) to dissect the role of TTBK2 in cilium stability. This system depletes TTBK2 levels after cilia formation, allowing us to assess the molecular changes to the assembled cilium over time. As a consequence of Ttbk2 deletion, the ciliary axoneme is destabilized and primary cilia are lost within 48-72 h following recombination. Axoneme destabilization involves an increased frequency of cilia breaks and a reduction in axonemal microtubule modifications. Cilia loss was delayed by using inhibitors that affect actin-based trafficking. At the same time, we find that TTBK2 is required to regulate the composition of the centriolar satellites and to maintain the basal body pools of intraflagellar transport proteins. Altogether, our results reveal parallel pathways by which TTBK2 maintains cilium stability.
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