Ciliary transcription factors and miRNAs precisely regulate Cp110 levels required for ciliary adhesions and ciliogenesis.
Upon cell cycle exit, centriole-to-basal body transition facilitates cilia formation. The centriolar protein Cp110 is a regulator of this process and cilia inhibitor, but its positive roles in ciliogenesis remain poorly understood. UsingXenopuswe show that Cp110 inhibits cilia formation at high levels, while optimal levels promote ciliogenesis. Cp110 localizes to cilia-forming basal bodies and rootlets, and is required for ciliary adhesion complexes that facilitate Actin interactions. The opposing roles of Cp110 in ciliation are generated in part by coiled-coil domains that mediate preferential binding to centrioles over rootlets. Because of its dual role in ciliogenesis, Cp110 levels must be precisely controlled. In multiciliated cells, this is achieved by both transcriptional and post-transcriptional regulation through ciliary transcription factors and microRNAs, which activate and represscp110to produce optimal Cp110 levels during ciliogenesis. Our data provide novel insights into how Cp110 and its regulation contribute to development and cell function.
Division of Genetics, Genomics and Development, Center for Integrative Genomics, Department of Molecular and Cell Biology, University of California, Berkeley, United States.
Peter
http://orcid.org/0000-0002-2332-6068
P
Walentek
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, United States.
Ian K
http://orcid.org/0000-0003-0075-8324
IK
Quigley
Division of Genetics, Genomics and Development, Center for Integrative Genomics, Department of Molecular and Cell Biology, University of California, Berkeley, United States.
Dingyuan I
DI
Sun
Division of Genetics, Genomics and Development, Center for Integrative Genomics, Department of Molecular and Cell Biology, University of California, Berkeley, United States.
Umeet K
UK
Sajjan
Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, United States.
Christopher
C
Kintner
Division of Genetics, Genomics and Development, Center for Integrative Genomics, Department of Molecular and Cell Biology, University of California, Berkeley, United States.
Richard M
http://orcid.org/0000-0001-8247-4880
RM
Harland
Foxj1; MCIDAS; RFX2; cell biology; centriole; cilia; developmental biology; focal adhesion; human; miR-34; miR-449; mucociliary epithelia; stem cells; xenopus