Intact intracellular tail is critical for proper functioning of the tumor-associated, hypoxia-regulated carbonic anhydrase IX

Abstract 

Carbonic anhydrase IX (CA IX) is a tumor-associated, hypoxia-induced enzyme involved in pH regulation and cell adhesion. Its catalytically active ectodomain (ECD) is linked to a transmembrane region and a short intracellular (IC) tail. Removal of the IC tail causes intracellular localization of CA IX. Mutations of basic amino acids within IC do not perturb the membrane position, but reduce shedding of the CA IX ectodomain as well as CA IX-mediated cell dissociation. Moreover, they abolish the CA IX capacity to acidify extracellular pH (pHe) and bind CA IX-selective sulfonamide inhibitor in hypoxia. These findings provide the first evidence for the critical contribution of the IC tail to the proper functioning of CA IX.

Structured summary

MINT-7293982: E-cadherin (uniprotkb:Q95LE0) and CA IX (genbank_protein_gi:223556027) colocalize (MI:0403) by fluorescence microscopy (MI:0416)

Abbreviations: CA IX, carbonic anhydrase IX, ECD, ectodomain, FITC-CAI, fluorescein-conjugated carbonic anhydrase inhibitor, MAb, monoclonal antibody, pHe, extracellular pH, TACE, TNFα-converting enzyme

Keywords: Carbonic anhydrase IX, pH regulation, Cell adhesion, Ectodomain shedding, Hypoxia, Acidosis