Arl13b regulates Shh signaling from both inside and outside the cilium.

ABSTRACT: The regulatory GTPase Arl13b localizes to primary cilia, where it regulates Sonic hedgehog (Shh) signaling. Missense mutations in ARL13B can cause the ciliopathy Joubert syndrome, while the mouse null allele is embryonic lethal. We used mouse embryonic fibroblasts as a system to determine the effects of Arl13b mutations on Shh signaling. We tested a total of seven different mutants, three JS-causing variants, two point mutants predicted to alter guanine nucleotide handling, one that disrupts cilia localization, and one that prevents palmitoylation and thus membrane binding, in assays of transcriptional and non-transcriptional Shh signaling. We found that mutations disrupting Arl13b's palmitoylation site, cilia localization signal, or GTPase handling altered the Shh response in distinct ass

SUBMITTER: Mariani LE 

PROVIDER: S-EPMC5170560 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature