Interplay between Septin 2 and Aquaporin 5 as a novel mechanism to modulate epithelial barrier function by regulation of microtubular stability.

Abstract

Airflow creates shear forces on the apical surface of airway epithelial cells, the effects of which are largely unknown. In isolated mouse trachea, airflow induced shear stress enhanced epithelial barrier function (evans blue dye‐4% albumin permeability). Primary human airway epithelial cells differentiated in an air‐interface were exposed to shear stress (3 dynes/cm2) using Krebs solution, causing increased barrier function (FITC‐dextran), and reduced the abundance of AQP5, an apical water channel, by sequential activation of TRPV4 and VGCC. With barrier enhancement we observe increased membrane associated septin 2 and destabilization of microtubules. Septin 2, known to mediate epithelial polarity in dividing cells by its interaction with microtubules, has not been previously implicated in altering monolayer barrier function. Our data suggests that AQP5 is a novel microtubule stabilizing protein and that regulation of AQP5 and Septin 2 modulate microtubule organization in response to shear stress, which is critical in regulating barrier function. This important homeostatic mechanism to regulate polarized epithelial responses to known stimuli such as EGF, IFNy and Substance P.