Actin-depolymerizing factor and cofilin-1 have unique and overlapping functions in regulating intestinal epithelial junctions and mucosal inflammation

14Citations
Citations of this article
19Readers
Mendeley users who have this article in their library.

Abstract

The actin cytoskeleton is a crucial regulator of the intestinal mucosal barrier, controlling the assembly and function of epithelial adherens and tight junctions (AJs and TJs). Junction-associated actin filaments are dynamic structures that undergo constant turnover. Members of the actin-depolymerizing factor (ADF) and cofilin protein family play key roles in actin dynamics by mediating filament severing and polymerization. We examined the roles of ADF and cofilin-1 in regulating the structure and functions of AJs and TJs in the intestinal epithelium. Knockdown of either ADF or cofilin-1 by RNA interference increased the paracellular permeability of human colonic epithelial cell monolayers to small ions. Additionally, cofilin-1, but not ADF, depletion increased epithelial permeability to large molecules. Loss of either ADF or cofilin-1 did not affect the steady-state morphology of AJs and TJs but attenuated de novo junctional assembly. The observed defects in AJ and TJ formation were accompanied by delayed assembly of the perijunctional filamentous actin belt. A total loss of ADF expression in mice did not result in a defective mucosal barrier or in spontaneous gut inflammation. However, ADF-null mice demonstrated increased intestinal permeability and exaggerated inflammation during dextran sodium sulfate-induced colitis. Our findings demonstrate novel roles for ADF and cofilin-1 in regulating the remodeling and permeability of epithelial junctions, as well as the role of ADF in limiting the severity of intestinal inflammation.

Cite

CITATION STYLE

APA

Wang, D., Naydenov, N. G., Feygin, A., Baranwal, S., Kuemmerle, J. F., & Ivanov, A. I. (2016). Actin-depolymerizing factor and cofilin-1 have unique and overlapping functions in regulating intestinal epithelial junctions and mucosal inflammation. American Journal of Pathology, 186(4), 844–858. https://doi.org/10.1016/j.ajpath.2015.11.023

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free