Keratins modulate colonocyte electrolyte transport via protein mistargeting

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Toivola DM, Krishnan S, Binder HJ, Singh SK, Omary MB
Publisher: ROCKEFELLER UNIV PRESS
Publication year: 2004
Journal: Journal of Cell Biology
Journal acronym: J CELL BIOL
Volume number: 164
Issue number: 6
Start page: 911
End page: 921
Number of pages: 11
ISSN: 0021-9525


Abstract

The function of intestinal keratins is unknown, although keratin 8 (K8)-null mice develop colitis, hyperplasia, diarrhea, and mistarget jejunal apical markers. We quantified the diarrhea in K8-null stool and examined its physiologic basis. Isolated crypt-units from K8-null and wild-type mice have similar viability. K8-null distal colon has normal tight junction permeability and paracellular transport but shows decreased short circuit current and net Na absorption associated with net Cl secretion, blunted intracellular Cl/HCO3-dependent pH regulation, hyperproliferation and enlarged goblet cells, partial loss of the membrane-proximal markers H,K-ATPase-beta and F-actin, increased and redistributed basolateral anion exchanger AE1/2 protein, and redistributed Na-transporter ENaC-gamma. Diarrhea and protein mistargeting are observed 1-2 d after birth while hyperproliferation/inflammation occurs later. The AE1/2 changes and altered intracellular pH regulation likely account, at least in part, for the ion transport defects and hyperproliferation. Therefore, colonic keratins have a novel function in regulating electrolyte transport, likely by targeting ion transporters to their cellular compartments.


Keywords

diarrhea, intermediate filaments, Intestine

Last updated on 2019-18-10 at 03:04