Format

Send to

Choose Destination
J Cell Biol. 2018 Sep 3;217(9):3255-3266. doi: 10.1083/jcb.201703196. Epub 2018 Jun 26.

Actin polymerization controls cilia-mediated signaling.

Author information

1
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA.
2
Department of Dermatology, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA.
3
Department of Dermatology, Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA oro@stanford.edu.
4
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA satwood@uci.edu.
5
Department of Dermatology, University of California, Irvine, Irvine, CA.
6
Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA.

Abstract

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 pinase 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 Smoothened-, 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.

PMID:
29945904
PMCID:
PMC6122990
[Available on 2019-03-03]
DOI:
10.1083/jcb.201703196

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center