title: Polarizing intestinal epithelial cells electrically through Ror2.
abstract: 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 to intestinal epithelial cells, to mimic the natural electric field created by the transepithelial potential difference, polarized phosphorylation of the actin-binding protein ezrin, increased expression of intestinal alkaline phosphatase (ALPI, a differentiation marker) and remodeled the actin cytoskeleton selectively on the cathode side. In addition, an applied electric field also activated ERK1/2 and LKB1 (also known as STK11), 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 electric field created by the transepithelial potential difference might act as an essential coordinating signal for apical membrane formation at a tissue level, through activation of LKB1 mediated by Ror2-ERK signaling.
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK Department of Dermatology, Department of Ophthalmology, Institute of Regenerative Cures, University of California, Davis, CA 95616, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Cao
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
authors.forename: Colin D
authors.initials: CD
authors.lastname: McCaig
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
authors.forename: Roderick H
authors.initials: RH
authors.lastname: Scott
authors.affiliation: Department of Bioengineering, University of California, Davis, CA 95616, USA.
authors.forename: Siwei
authors.initials: S
authors.lastname: Zhao
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Milne
authors.affiliation: Hubrecht Institute for Developmental Biology and Stem Cell Research & University Medical Centre Utrecht, 3584 CT Utrecht, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.affiliation: Department of Dermatology, Department of Ophthalmology, Institute of Regenerative Cures, University of California, Davis, CA 95616, USA jin.pu@abdn.ac.uk minzhao@ucdavis.edu.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK jin.pu@abdn.ac.uk minzhao@ucdavis.edu.
authors.forename: Jin
authors.initials: J
authors.lastname: Pu
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D008841:Actin Cytoskeleton / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D016764:Cell Polarity / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004560:Electricity; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology* / Q000648:ultrastructure; D020935:MAP Kinase Signaling System / Q000235:genetics; D008871:Microvilli / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism*; D019076:Transgenes / Q000235:genetics; D000099149:Ezrin
chemical_list: D000091162:AMP-Activated Protein Kinase Kinases; D000469:Alkaline Phosphatase; D003598:Cytoskeletal Proteins; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D000099149:Ezrin; C078717:ROR2 protein, human; C109790:STK11 protein, human
keywords: Cell polarization; Electric field; Intestinal epithelial cells; Ror2; Transepithelial potential difference