title: The AE gene family of Cl/HCO3- exchangers.
abstract: Tubular acid-base transport regulates systemic acid-base balance. Transepithelial acid-base transport across nephron segments requires the coordinated control of intracellular pH and cellular volume by transporters of protons and bicarbonate. Bicarbonate transporter polypeptides are encoded by at least two gene families, SLC4 and SLC26. The SLC4 gene family includes at least three Na()+)-independent chloride-bicarbonate exchanger genes and multiple Na(+)-bicarbonate cotransporter and Na(+)-dependent anion exchanger genes. The most extensively studied among them are the Na(+)-independent anion exchangers, AE1, AE2, and AE3, all of which are expressed in kidney. The AE1 gene encodes eAE1 (band 3), the major intrinsic protein of the erythrocyte, as well as kAE1, the basolateral Cl/HCO3 exchanger of the acid-secreting Type A intercalated cell. Mutations in AE1 are responsible for some forms of heritable distal renal tubular acidosis. The widely expressed AE2 anion exchanger participates in recovery from alkaline load and in regulatory cell volume increase following shrinkage. AE2 can also be regulated by ammonium ion. These properties are not shared by the closely related AE1 anion exchanger. Less is known about AE3 in kidney. Structure-function studies of recombinant proteins involving chimeras, deletions, and point mutations have delineated regions of AE2 which are important in exhibition of the regulatory properties absent from AE1. These include regions of the transmembrane domain and the N-terminal cytoplasmic domain. Noncontiguous regions in the middle of the N-terminal cytoplasmic domain are of particular importance for acute regulation by several types of stimulus.
authors.affiliation: Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. salper@caregroup.harvard.edu
authors.forename: Seth L
authors.initials: SL
authors.lastname: Alper
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Darman
authors.forename: Marina N
authors.initials: MN
authors.lastname: Chernova
authors.forename: Neera K
authors.initials: NK
authors.lastname: Dahl
mesh_terms: D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics / Q000502:physiology; D027321:Anion Transport Proteins; D017920:Antiporters / Q000235:genetics / Q000502:physiology; D027963:Chloride-Bicarbonate Antiporters / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D005810:Multigene Family; D017433:Protein Structure, Secondary; D064606:SLC4A Proteins; D013329:Structure-Activity Relationship
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D027321:Anion Transport Proteins; D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; D008565:Membrane Proteins; D064606:SLC4A Proteins; C489237:SLC4A3 protein, human