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 (pages 5049–5063)
Mingmin Chen, Ayesha Sultan, Ayhan Cinar, Sunil Yeruva, Brigitte Riederer, Anurag Kumar Singh, Junhua Li, Janina Bonhagen, Gang Chen, Chris Yun, Mark Donowitz, Boris Hogema, Hugo deJonge and Ursula Seidler
Article first published online: 15 DEC 2010 | DOI: 10.1113/jphysiol.2010.198721
During digestion, the distal intestine needs to reabsorb large quantities of salt and water that have been secreted into the gastrointestinal lumen by more proximal organs or are ingested through the mouth. We here show that the major salt absorptive transporter, sodium/hydrogen exchanger isoform 3 (NHE3), requires the PDZ-adaptor protein NHERF2 to determine its localization along the terminal web-microvillar axis in the apical pole of the enterocyte. The NHERF-2 deficient murine intestine has also lost the ability of certain secretagogues to inhibit NHE3 absorptive function and thereby to cause diarrhoea. NHERF-2 is therefore an important regulator of intestinal fluid transport, and is an interesting drug target, encoded by a potential disease-causing modifier gene.