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Cell. 2012 Nov 9;151(4):847-858. doi: 10.1016/j.cell.2012.10.010.

The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis.

Author information

1
Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10065, USA.
2
Developmental Biology Program, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10065, USA. Electronic address: k-anderson@sloankettering.edu.

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.

PMID:
23141541
PMCID:
PMC3496184
DOI:
10.1016/j.cell.2012.10.010
[Indexed for MEDLINE]
Free PMC Article

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