ArticlePLoS genetics2018
Spinocerebellar ataxia type 11-associated alleles of Ttbk2 dominantly interfere with ciliogenesis and cilium stability.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 58 citations in OpenAlex.
- Review
- Pathophysiological significance of cholesterol in ciliopathies.Fujita medical journal · 2026Article
- Missense variant in TTBK2 kinase domain causes loss of function and impaired protein phosphorylation.Scientific reports · 2025Article
- Phosphorylation at the Helm: Kinase-Mediated Regulation of Primary Cilia Assembly and Disassembly.Cytoskeleton (Hoboken, N.J.) · 2025Review
- Identification of New Ciliary Signaling Pathways in the Brain and Insights into Neurological Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Assembly and mother centriole recruitment of IFT-B subcomplexes to form IFT-B holocomplex.Cell structure and function · 2025Article
- TTBK2 affects sperm quality by regulating the expression of centrosomal proteins and flagellar transporters during spermiogenesis in mice.Molecular human reproduction · 2025Article
- CCDC66 regulation of cytoskeleton and cilia stability is important for signaling and epithelial organization.PLoS biology · 2025Article
- Coordinated roles of the CEP164 homodimer and TTBK2 are required for recruitment of the IFT machinery to the mother centriole for ciliogenesis.Molecular biology of the cell · 2025Article
- Cilia at the crossroad: convergence of regulatory mechanisms to govern cilia dynamics during cell signaling and the cell cycle.Cell & bioscience · 2025Review
- Non-canonical CDK6 activity promotes cilia disassembly by suppressing axoneme polyglutamylation.The Journal of cell biology · 2025Article
- Loss of Kat2b impairs intraflagellar transport and the Hedgehog signaling pathway in primary cilia.Scientific reports · 2025Article
- Spinocerebellar ataxia type 11 (SCA11): TTBK2 variants, functions and associated disease mechanisms.Cerebellum (London, England) · 2024Review
- Emerging insights into CP110 removal during early steps of ciliogenesis.Journal of cell science · 2024Review
- Illumination of understudied ciliary kinases.Frontiers in molecular biosciences · 2024Review
- Article
- Tau tubulin kinase 1 and 2 regulate ciliogenesis and human pluripotent stem cells-derived neural rosettes.Scientific reports · 2023Article
- Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis.Scientific reports · 2023Article
- TTBK2 controls cilium stability by regulating distinct modules of centrosomal proteins.Molecular biology of the cell · 2023Article
- Viewpoint: spinocerebellar ataxias as diseases of Purkinje cell dysfunction rather than Purkinje cell loss.Frontiers in molecular neuroscience · 2023Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Spinocerebellar ataxia type 11 (SCA11) is a rare, dominantly inherited human ataxia characterized by atrophy of Purkinje neurons in the cerebellum. SCA11 is caused by mutations in the gene encoding the Serine/Threonine kinase Tau tubulin kinase 2 (TTBK2) that result in premature truncations of the protein. We previously showed that TTBK2 is a key regulator of the assembly of primary cilia in vivo. However, the mechanisms by which the SCA11-associated mutations disrupt TTBK2 function, and whether they interfere with ciliogenesis were unknown. In this work, we present evidence that SCA11-associated mutations are dominant negative alleles and that the resulting truncated protein (TTBK2SCA11) interferes with the function of full length TTBK2 in mediating ciliogenesis. A Ttbk2 allelic series revealed that upon partial reduction of full length TTBK2 function, TTBK2SCA11 can interfere with the activity of the residual wild-type protein to decrease cilia number and interrupt cilia-dependent Sonic hedgehog (SHH) signaling. Our studies have also revealed new functions for TTBK2 after cilia initiation in the control of cilia length, trafficking of a subset of SHH pathway components, including Smoothened (SMO), and cilia stability. These studies provide a molecular foundation to understand the cellular and molecular pathogenesis of human SCA11, and help account for the link between ciliary dysfunction and neurodegenerative diseases.
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