AE1mediated

AE1mediated refers to the cellular processes driven by the anion exchanger 1 (AE1), a membrane transporter that exchanges chloride (Cl−) for bicarbonate (HCO3−) across the plasma membrane. AE1 is encoded by the SLC4A1 gene and is highly expressed in red blood cells, with additional expression in kidney basolateral membranes and select epithelia. In erythrocytes, AE1 mediates the chloride shift (Hamburger phenomenon) that accompanies CO2 transport from tissues to the lungs: CO2 diffuses into red blood cells and is converted to bicarbonate and protons by carbonic anhydrase II; bicarbonate is exchanged for chloride via AE1, helping move bicarbonate out of cells and chloride in; at the lungs, the process reverses to release CO2.

In renal and other epithelial contexts, AE1 participates in basolateral bicarbonate transport and urine acidification, contributing to systemic acid-base homeostasis by reclaiming bicarbonate and balancing chloride exchanges. Molecularly, AE1 is a multi-pass transmembrane protein with several transmembrane segments; its cytoplasmic N- and C- termini interact with the cytoskeleton, notably ankyrin and spectrin, anchoring the transporter to the membrane skeleton.

Clinical relevance includes mutations in SLC4A1, which can cause distal renal tubular acidosis and various red blood cell membrane disorders such as Southeast Asian ovalocytosis and hereditary spherocytosis. Regulation of AE1 activity is influenced by intracellular pH, phosphorylation state, and interactions with cytoskeletal components, reflecting its integration into cellular pH control and membrane stability networks.