The spinocerebellar ataxia-associated gene tau tubulin kinase 2 controls the initiation of ciliogenesis Journal Article
| Authors: | Goetz, S. C.; Liem, K. F. Jr; Anderson, K. V. |
| Article Title: | The spinocerebellar ataxia-associated gene tau tubulin kinase 2 controls the initiation of ciliogenesis |
| Abstract: | The primary cilium has critical roles in human development and disease, but the mechanisms that regulate ciliogenesis are not understood. Here, we show that Tau tubulin kinase 2 (TTBK2) is a dedicated regulator of the initiation of ciliogenesis in vivo. We identified a null allele of mouse Ttbk2 based on loss of Sonic hedgehog activity, a signaling pathway that requires the primary cilium. Despite a normal basal body template, Ttbk2 mutants lack cilia. TTBK2 acts at the distal end of the basal body, where it promotes the removal of CP110, which caps the mother centriole, and promotes recruitment of IFT proteins, which build the ciliary axoneme. Dominant truncating mutations in human TTBK2 cause spinocerebellar ataxia type 11 (SCA11); these mutant proteins do not promote ciliogenesis and inhibit ciliogenesis in wild-type cells. We propose that cell-cycle regulators target TTBK2 to the basal body, where it modifies specific targets to initiate ciliogenesis. © 2012 Elsevier Inc. |
| Keywords: | signal transduction; gene mutation; mutation; nonhuman; protein function; mouse; animals; cell cycle proteins; mice; gene; embryo; sonic hedgehog protein; hedgehog proteins; in vivo study; protein-serine-threonine kinases; cell cycle regulation; eukaryotic flagellum; cilia; ciliary motility; centriole; axoneme; microtubule-associated proteins; spinocerebellar degeneration; tau tubulin kinase 2 gene; spinocerebellar ataxias |
| Journal Title: | Cell |
| Volume: | 151 |
| Issue: | 4 |
| ISSN: | 0092-8674 |
| Publisher: | Cell Press |
| Date Published: | 2012-11-09 |
| Start Page: | 847 |
| End Page: | 858 |
| Language: | English |
| DOI: | 10.1016/j.cell.2012.10.010 |
| PROVIDER: | scopus |
| PMCID: | PMC3496184 |
| PUBMED: | 23141541 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 3 December 2012" - "CODEN: CELLB" - "Source: Scopus" |
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