Tetratricopeptide Repeat Domain Protein 21B (TTC21B)

Aln mutant cilia have bulb-like structures at their tips in which intraflagellar transport (IFT) proteins such as Ift88 are sequestered, characteristic of Chlamydomonas reinhardtii and Caenorhabditis elegans retrograde IFT mutants. Ttc21b, in mouse intermedullary collecting duct cells expressing an Ift88-enhanced yellow fluorescent protein fusion recapitulated the aln-mutant cilial phenotype, and live imaging of these cells revealed impaired retrograde intraflagellar transport. In contrast to previously described IFT mutants, Smoothened and full-length glioblastoma (GLI) proteins localize to aln-mutant cilia. Specifically, the aln mutation uncouples the roles of anterograde and retrograde transport in Sonic hedgehog signaling, suggesting that anterograde IFT is required for GLI activation and that retrograde IFT modulates this event.