Human Thyroperoxidase in Its Alternatively Spliced Form (TPO2) Is Enzymatically Inactive and Exhibits Changes in Intracellular Processing and Trafficking

摘要: Abstract Thyroid peroxidase (TPO1) is a membrane-bound heme-containing glycoprotein that catalyzes the synthesis of thyroid hormones. We generated stable cell lines expressing TPO1 and alternatively spliced isoform TPO2. Pulse-chase studies showed TPO2 half-life was dramatically decreased as compared with TPO1. The sensitivity to endo-β-N-acetylglucosaminidase H indicated protein processed through endoplasmic reticulum bears high mannose-type structures. Cell surface biotinylation experiments two isoforms also differ in their intracellular trafficking. totally retained cell, whereas 15% reached surface. inability come out compartments related structural changes molecule. Evidence these obtained lack recognition by half 13 TPO monoclonal antibodies tested immunoprecipitation experiments. Our data suggest because an improper folding, trapped rapidly degraded. failure incorporation [14C]aminolevulinic acid cultured cells did not bind heme, did. This result confirmed guaiacol assay showing enzymatically inactive.