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Vol. 20, Issue 1, 102-113, January 1, 2009

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Deciliation Is Associated with Dramatic Remodeling of Epithelial Cell Junctions and Surface Domains

Christian E. Overgaard^*, Kaitlin M. Sanzone^*, Krystle S. Spiczka^*, David R. Sheff, Alexander Sandra^*, and Charles Yeaman^*

Departments of *Anatomy and Cell Biology and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242

Submitted July 18, 2008; Revised October 23, 2008; Accepted October 30, 2008
Monitoring Editor: Asma Nusrat

Stress-induced shedding of motile cilia (autotomy) has been documented in diverse organisms and likely represents a conserved cellular reaction. However, little is known about whether primary cilia are shed from mammalian epithelial cells and what impact deciliation has on polarized cellular organization. We show that several chemically distinct agents trigger autotomy in epithelial cells. Surprisingly, deciliation is associated with a significant, but reversible increase in transepithelial resistance. This reflects substantial reductions in tight junction proteins associated with "leaky" nephron segments (e.g., claudin-2). At the same time, apical trafficking of gp80/clusterin and gp114/CEACAM becomes randomized, basal-lateral delivery of Na,K-ATPase is reduced, and expression of the nonciliary apical protein gp135/podocalyxin is greatly decreased. However, ciliogenesis-impaired MDCK cells do not undergo continual junction remodeling, and mature cilia are not required for autotomy-associated remodeling events. Deciliation and epithelial remodeling may be mechanistically linked processes, because RNAi-mediated reduction of Exocyst subunit Sec6 inhibits ciliary shedding and specifically blocks deciliation-associated down-regulation of claudin-2 and gp135. We propose that ciliary autotomy represents a signaling pathway that impacts the organization and function of polarized epithelial cells.

Address correspondence to: Charles Yeaman (charles-yeaman{at}uiowa.edu)