Regulation of intracellular pH by a neuronal homolog of the erythrocyte anion exchanger.
We have isolated AE3, a novel gene expressed primarily in brain neurons and in heart. The predicted AE3 polypeptide shares a high degree of identity with the anion exchange and cytoskeletal binding domains of the erythrocyte band 3 protein. Expression of AE3 cDNA in COS cells leads to chronic cytoplasmic acidification and to chloride- and bicarbonate-dependent changes in intracellular pH, confirming that this gene product is an anion exchanger. Characterization of an AE3 mutant lacking the NH2-terminal 645 amino acids demonstrates that the COOH-terminal half of the polypeptide is both necessary and sufficient for correct insertion into the plasma membrane and for anion exchange activity. The NH2-terminal domain may play a role in regulating the activity of the exchanger and may be involved in the structural organization of the cytoskeleton in neurons.
Kopito
R R
RR
Department of Biological Sciences, Stanford University, California 94305-5020.
Lee
B S
BS
Simmons
D M
DM
Lindsey
A E
AE
Morgans
C W
CW
Schneider
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000235:genetics*; D017920:Antiporters; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D004912:Erythrocytes / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression; D005796:Genes; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D001457:Anion Exchange Protein 1, Erythrocyte; D017920:Antiporters; D008565:Membrane Proteins; D012333:RNA, Messenger; C062002:Slc4a3 protein, mouse