Alternatively spliced form of human thyroperoxidase, TPOzanelli: activity, intracellular trafficking, and role in hormonogenesis

Biochemistry
P Niccoli-SireJean-Louis Franc

Abstract

Thyroperoxidase (TPO), a type I transmembrane heme containing glycoprotein, catalyzes iodide organification and thyroid hormone synthesis. One of the two main alternatively spliced forms of this enzyme, TPOzanelli, which is present in Graves's disease thyroid tissue, has a cytoplasmic domain completely modified. In the first stage of this study, the results of RT-PCR experiments showed that the TPOzanelli mRNA is present in normal thyroid tissue. We then generated CHO cell lines expressing the wild-type TPO (TPO1) and the alternatively spliced form TPOzanelli. Upon investigating a panel of 12 mAbs directed against the extracellular domain of TPO1 and sera from patients with a high titer of TPO autoantibodies, we observed that (i) the three-dimensional structure of this domain is similar in both isoforms; (ii) the autoantibodies recognize TPOzanelli as well as TPO1. The results of pulse chase and cell surface biotinylation experiments showed that the TPOzanelli has a shorter half-life (7 versus 11 h) and is expressed at the cell surface in lesser amounts than TPO1 (7 versus 15%). The total enzymatic activity and cell surface activity were determined in CHO cells expressing TPO1 and TPOzanelli, and TPO1 and TPOzanelli were found ...Continue Reading

References

Jun 1, 1996·Archives of Biochemistry and Biophysics·A TaurogD R Doerge

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Citations

Oct 12, 2013·International Journal of Cancer. Journal International Du Cancer·I MullerM E Ludgate
Jan 20, 2005·Gene·Stefan StammHermona Soreq
Aug 16, 2005·Archives of Biochemistry and Biophysics·Jean Ruf, Pierre Carayon
Apr 20, 2014·BioMed Research International·Ching Chin LeeSarni Mat Junit
Jun 16, 2004·Biochimica Et Biophysica Acta·Valérie Le FournJean-Louis Franc
Dec 22, 2004·Arquivos brasileiros de endocrinologia e metabologia·Mário VaismanDenise P Carvalho

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