title: Governing effect of regulatory proteins for Cl(-)/HCO3(-) exchanger 2 activity.
abstract: Anion exchanger 2 (AE2) has a critical role in epithelial cells and is involved in the ionic homeostasis such as Cl(-) uptake and HCO3(-) secretion. However, little is known about the regulatory mechanism of AE2. The main goal of the present study was to investigate potential regulators, such as spinophilin (SPL), inositol-1,4,5-trisphosphate [IP3] receptors binding protein released with IP3 (IRBIT), STE20/SPS1-related proline/alanine-rich kinase (SPAK) kinase, and carbonic anhydrase XII (CA XII). We found that SPL binds to AE2 and markedly increased the Cl(-)/HCO3(-) exchange activity of AE2. Especially SPL 1-480 domain is required for enhancing AE2 activity. For other regulatory components that affect the fidelity of fluid and HCO3(-) secretion, IRBIT and SPAK had no effect on the activity of AE2 and no protein-protein interaction with AE2. It has been proposed that CA activity is closely associated with AE activity. In this study, we provide evidence that the basolateral membrane-associated CA isoform CA XII significantly increased the activity of AE2 and co-localized with AE2 to the plasma membrane. Collectively, SPL and CA XII enhanced the Cl(-)/HCO3(-) exchange activity of AE2. The modulating action of these regulatory proteins could serve as potential therapeutic targets for secretory diseases mediated by AE2.
authors.affiliation: a Department of Physiology , Graduate School of Medicine, Gachon University , South Korea.
authors.forename: Yon Soo
authors.initials: YS
authors.lastname: Jeong
authors.affiliation: a Department of Physiology , Graduate School of Medicine, Gachon University , South Korea.
authors.forename: Jeong Hee
authors.initials: JH
authors.lastname: Hong
mesh_terms: D001639:Bicarbonates / Q000378:metabolism*; D002256:Carbonic Anhydrases / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D001639:Bicarbonates; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D002256:Carbonic Anhydrases
keywords: IRBIT; SPAK; anion exchanger 2; carbonic anhydrase XII; fluid secretion; spinophilin