09 2018
Journal of Cell Biology published our work on actin polymerization controlling Hedgehog signaling
Primary cilia are polarized organelles that allow detection of extracellular signals such as Hedgehog (Hh). How the
cytoskeleton supporting the cilium generates and maintains a structure that finely tunes cellular response remains unclear. Here we find that regulation of actin polymerization controls primary cilia
and Hh signaling. Disrupting actin polymerization, or knockdown of N-WASp/Arp3, increases ciliation frequency, axoneme length, and Hh signaling. Cdc42, a potent actin regulator, recruits both atypical
Protein Kinase C iota/lambda (aPKC) and Missing-in-Metastasis (MIM) to the basal body to maintain actin polymerization and restrict axoneme length. Transcriptome analysis implicates the Src pathway
as a major aPKC effector. aPKC promotes whereas MIM antagonizes Src activity to maintain proper levels of primary cilia, actin polymerization, and Hh signaling. Hh pathway activation requires Smo,
Gli, and Gli1-specific activation by aPKC. Surprisingly, longer axonemes can amplify Hh signaling except when aPKC is disrupted, reinforcing the importance of the Cdc42-aPKC-Gli axis in actin-dependent
regulation of primary cilia signaling.
