title: Shank2 associates with and regulates Na+/H+ exchanger 3.
abstract: Na+/H+ exchanger 3 (NHE3) plays a pivotal role in transepithelial Na+ and HCO3(-) absorption across a wide range of epithelia in the digestive and renal-genitourinary systems. Accumulating evidence suggests that PDZ-based adaptor proteins play an important role in regulating the trafficking and activity of NHE3. A search for NHE3-binding modular proteins using yeast two-hybrid assays led us to the PDZ-based adaptor Shank2. The interaction between Shank2 and NHE3 was further confirmed by immunoprecipitation and surface plasmon resonance studies. When expressed in PS120/NHE3 cells, Shank2 increased the membrane expression and basal activity of NHE3 and attenuated the cAMP-dependent inhibition of NHE3 activity. Furthermore, knock-down of native Shank2 expression in Caco-2 epithelial cells by RNA interference decreased NHE3 protein expression as well as activity but amplified the inhibitory effect of cAMP on NHE3. These results indicate that Shank2 is a novel NHE3 interacting protein that is involved in the fine regulation of transepithelial salt and water transport through affecting NHE3 expression and activity.
authors.affiliation: Department of Pharmacology, Brain Korea 21 Project for Medical Science, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: WonSun
authors.initials: W
authors.lastname: Han
authors.forename: Kyung Hwan
authors.initials: KH
authors.lastname: Kim
authors.forename: Min Jae
authors.initials: MJ
authors.lastname: Jo
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Jinhee
authors.initials: J
authors.lastname: Yang
authors.forename: R Brian
authors.initials: RB
authors.lastname: Doctor
authors.forename: Orson W
authors.initials: OW
authors.lastname: Moe
authors.forename: Jinu
authors.initials: J
authors.lastname: Lee
authors.forename: Eunjoon
authors.initials: E
authors.lastname: Kim
authors.forename: Min Goo
authors.initials: MG
authors.lastname: Lee
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D006224:Cricetinae; D017353:Gene Deletion; D017930:Genes, Reporter; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D014162:Transfection
chemical_list: D009419:Nerve Tissue Proteins; C122162:SHANK2 protein, human; D017923:Sodium-Hydrogen Exchangers