Loss of PDZ-adaptor protein NHERF2 affects membrane localization and cGMP- and [Ca2+]- but not cAMP-dependent regulation of Na+/H+exchanger 3 in murine intestine
Open Access
- 15 December 2010
- journal article
- Published by Wiley in The Journal of Physiology
- Vol. 588 (24), 5049-5063
- https://doi.org/10.1113/jphysiol.2010.198721
Abstract
Trafficking and regulation of the epithelial brush border membrane (BBM) Na+/H+ exchanger 3 (NHE3) in the intestine involves interaction with four different members of the NHERF family in a signal‐dependent and possibly segment‐specific fashion. The aim of this research was to study the role of NHERF2 (E3KARP) in intestinal NHE3 BBM localization and second messenger‐mediated and receptor‐mediated inhibition of NHE3. Immunolocalization of NHE3 in WT mice revealed predominant microvillar localization in jejunum and colon, a mixed distribution in the proximal ileum but localization near the terminal web in the distal ileum. The terminal web localization of NHE3 in the distal ileum correlated with reduced acid‐activated NHE3 activity (fluorometrically assessed). NHERF2 ablation resulted in a shift of NHE3 to the microvilli and higher basal fluid absorption rates in the ileum, but no change in overall NHE3 protein or mRNA expression. Forskolin‐induced NHE3 inhibition was preserved in the absence of NHERF2, whereas Ca2+ ionophore‐ or carbachol‐mediated inhibition was abolished. Likewise, Escherichia coli heat stable enterotoxin peptide (STp) lost its inhibitory effect on intestinal NHE3. It is concluded that in native murine intestine, the NHE3 adaptor protein NHERF2 plays important roles in tethering NHE3 to a position near the terminal web and in second messenger inhibition of NHE3 in a signal‐ and segment‐specific fashion, and is therefore an important regulator of intestinal fluid transport.Keywords
This publication has 53 references indexed in Scilit:
- NHE3 mobility in brush borders increases upon NHERF2-dependent stimulation by lyophosphatidic acidJournal of Cell Science, 2010
- The switch of intestinal Slc26 exchangers from anion absorptive to HCO3−secretory mode is dependent on CFTR anion channel functionAmerican Journal of Physiology-Cell Physiology, 2010
- Lysophosphatidic Acid Stimulates the Intestinal Brush Border Na+/H+ Exchanger 3 and Fluid Absorption via LPA5 and NHERF2Gastroenterology, 2010
- Angiotensin II stimulates trafficking of NHE3, NaPi2, and associated proteins into the proximal tubule microvilliAmerican Journal of Physiology-Renal Physiology, 2010
- NHERF3 (PDZK1) Contributes to Basal and Calcium Inhibition of NHE3 Activity in Caco-2BBe CellsPublished by Elsevier BV ,2009
- Renal NHE3 and NaPi2 partition into distinct membrane domainsAmerican Journal of Physiology-Cell Physiology, 2009
- Differential roles of NHERF1, NHERF2, and PDZK1 in regulating CFTR-mediated intestinal anion secretion in miceJCI Insight, 2009
- NHE3 inhibition by cAMP and Ca2+ is abolished in PDZ‐domain protein PDZK1‐deficient murine enterocytesThe Journal of Physiology, 2007
- Autonomic nervous system and secretion across the intestinal mucosal surfaceAutonomic Neuroscience, 2007
- How do the rotavirus NSP4 and bacterial enterotoxins lead differently to diarrhea?Virology Journal, 2007