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Intact intracellular tail is critical for proper functioning of the tumor-associated, hypoxia-regulated carbonic anhydrase IX |
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| Authors: | Alzbeta Hulikova Eliska Svastova Robert Brasseur Claudiu T Supuran Jaromir Pastorek Silvia Pastorekova |
| Institution: | a Institute of Virology, Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovak Republic b Centre de Biophysique Moléculaire Numérique, Faculté des Sciences Agronomiques de Gembloux, B-5030 Gembloux, Belgium c Biologie cellulaire et moléculaire, Faculté des Sciences Agronomiques de Gembloux, B-5030 Gembloux, Belgium d Universita degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy |
| 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 summaryMINT-7293982: E-cadherin (uniprotkb:Q95LE0) and CA IX (genbank_protein_gi:223556027) colocalize (MI:0403) by fluorescence microscopy (MI:0416) |
| Keywords: | CA IX carbonic anhydrase IX ECD ectodomain FITC-CAI fluorescein-conjugated carbonic anhydrase inhibitor MAb monoclonal antibody pHe extracellular pH TACE TNFα-converting enzyme |
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