Polarizing intestinal epithelial cells electrically through Ror2

• Published in: Journal of cell science Vol. 127; no. Pt 15; pp. 3233 - 3239
• Main Authors: Cao, Lin, McCaig, Colin D, Scott, Roderick H, Zhao, Siwei, Milne, Gillian, Clevers, Hans, Zhao, Min, Pu, Jin
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists 01.08.2014
• Subjects: Actin Cytoskeleton - metabolism; Alkaline Phosphatase - genetics; Alkaline Phosphatase - metabolism; Cell Line; Cell Polarity - genetics; Cytoskeletal Proteins - metabolism; Electricity; Humans; Intestinal Mucosa - physiology; Intestinal Mucosa - ultrastructure; MAP Kinase Signaling System - genetics; Microvilli - ultrastructure; Mutation - genetics; Protein-Serine-Threonine Kinases - metabolism; Receptor Tyrosine Kinase-like Orphan Receptors - genetics; Receptor Tyrosine Kinase-like Orphan Receptors - metabolism; RNA, Small Interfering - genetics; Short Report; Transgenes - genetics; Electric field; Ror2; Cell polarization; Transepithelial potential difference; Intestinal epithelial cells
• ISSN: 0021-9533; 1477-9137; 1477-9137
• DOI: 10.1242/jcs.146357

The apicobasal polarity of enterocytes determines where the brush border membrane (apical membrane) will form, but how this apical membrane faces the lumen is not well understood. The electrical signal across the epithelium could serve as a coordinating cue, orienting and polarizing enterocytes. Here we show that applying a physiological electric field (EF) to intestinal epithelial cells, to mimic the natural EF created by the transepithelial potential difference, directed phosphorylation of the actin-binding protein ezrin, increased expression of intestinal alkaline phosphatase (ALPI, a differentiation marker) and remodelled the actin cytoskeleton selectively on the cathode side. In addition, an applied EF also activated ERK1/2 and LKB1, key molecules in apical membrane formation. Disruption of the tyrosine-protein kinase transmembrane receptor Ror2 suppressed activation of ERK1/2 and LKB1 significantly and subsequently inhibited apical membrane formation in enterocytes. Our findings indicate that the endogenous EF created by the TEP may act as an essential coordinating signal for apical membrane formation at a tissue level, through activation of LKB1 mediated by Ror2/ERK signalling.