title: NHE3 regulatory complexes.
abstract: The epithelial brush border Na/H exchanger NHE3 is active under basal conditions and functions as part of neutral NaCl absorption in the intestine and renal proximal tubule, where it accounts for the majority of total Na absorbed. NHE3 is highly regulated. Both stimulation and inhibition occur post-prandially. This digestion related regulation of NHE3 is mimicked by multiple extracellular agonists and intracellular second messengers. The regulation of NHE3 depends on its C-terminal cytoplasmic domain, which acts as a scaffold to bind multiple regulatory proteins and links NHE3 to the cytoskeleton. The cytoskeletal association occurs by both direct binding to ezrin and by indirect binding via ezrin binding to the C-terminus of the multi-PDZ domain containing proteins NHERF1 and NHERF2. This is a review of the domain structure of NHE3 and of the scaffolding function and role in the regulation of NHE3 of the NHE3 C-terminal domain.
authors.affiliation: Johns Hopkins University School of Medicine, 720 Rutland Avenue Baltimore, MD 21205, USA. mdonowit@jhmi.edu
authors.forename: Mark
authors.initials: M
authors.lastname: Donowitz
authors.forename: Sachin
authors.initials: S
authors.lastname: Mohan
authors.forename: Cindy Xinjun
authors.initials: CX
authors.lastname: Zhu
authors.forename: Tian-E
authors.initials: TE
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Lin
authors.forename: Boyoung
authors.initials: B
authors.lastname: Cha
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Zachos
authors.forename: Rakhilya
authors.initials: R
authors.lastname: Murtazina
authors.forename: Rafiquel
authors.initials: R
authors.lastname: Sarker
authors.forename: Xuhang
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism; D008322:Mammals; D008958:Models, Molecular; D011487:Protein Conformation; D012965:Sodium Chloride / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry / Q000378:metabolism*
chemical_list: C000613385:SLC9A3 protein, human; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D012965:Sodium Chloride