Keratins modulate colonocyte electrolyte transport via protein mistargeting

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Toivola DM, Krishnan S, Binder HJ, Singh SK, Omary MB
Förläggare: ROCKEFELLER UNIV PRESS
Publiceringsår: 2004
Tidskrift: Journal of Cell Biology
Tidskriftsakronym: J CELL BIOL
Volym: 164
Nummer: 6
Artikelns första sida, sidnummer: 911
Artikelns sista sida, sidnummer: 921
Antal sidor: 11
ISSN: 0021-9525


Abstrakt

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.


Nyckelord

diarrhea, intermediate filaments, Intestine

Senast uppdaterad 2019-07-12 vid 03:05