RhoA-mediated apical actin enrichment is required for ciliogenesis and promoted by Foxj1

Jiehong Pan, Yingjian You, Tao Huang, Steven L. Brody

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

Programs that direct cellular differentiation are dependent on the strict temporal expression of regulatory factors that can be provided by Rho GTPases. Ciliogenesis is a complex sequence of events involving the generation and docking of basal bodies at the apical membrane, followed by ciliary axoneme generation. Although a cilia proteome has been assembled, programs that direct ciliated cell differentiation are not well established, particularly in mammalian systems. Using mouse primary culture airway epithelial cells, we identified a critical stage of ciliogenesis requiring the temporal establishment of an apical web-like structure of actin for basal body docking and subsequent axoneme growth. Apical web formation and basal body docking were prevented by interruption of actin remodeling and were dependent on RhoA activation. Additional evidence for this program was provided by analysis of Foxj1-null mice that failed to dock basal bodies and lacked apical actin. Foxj1 expression coincided with actin web formation, activated RhoA and RhoB, and persisted despite RhoA inhibition, suggesting that Foxj1 promoted RhoA during ciliogenesis. Apical ezrin localization was also dependent on Foxj1, actin remodeling, and RhoA, but was not critical for ciflogenesis. Thus, temporal Foxj1 and RhoA activity are essential regulatory events for cytoskeletal remodeling during mammalian ciliogenesis.

Original languageEnglish
Pages (from-to)1868-1876
Number of pages9
JournalJournal of cell science
Volume120
Issue number11
DOIs
StatePublished - Jun 1 2007

Keywords

  • Airway epithelial cells
  • Basal bodies
  • Cilia
  • GTPase
  • Mouse

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