Secretion of thioredoxin by normal and neoplastic cells through a leaderless secretory pathway.

TLDR

Thioredoxin, an intracellular disulfide‑reducing enzyme lacking a signal sequence, has been found to function extracellularly. We demonstrate that thioredoxin is actively secreted by normal and transformed cells via a leaderless, non‑classical ER‑Golgi pathway that is insensitive to brefeldin A and dinitrophenol, shares features with the IL‑1β alternative route, is methylamine‑sensitive, and is not detected in membrane compartments, with transfection experiments confirming its extracellular release while pro‑IL‑1β is not.

Abstract

Thioredoxin, despite its function as an intracellular disulfide reducing enzyme and its lack of a signal sequence, has been found to play some roles extracellularly. Here we show that thioredoxin is actively secreted by a variety of normal and transformed cells, including fibroblasts, airway epithelial cells, and activated B and T lymphocytes. Neither brefeldin A nor dinitrophenol, two drugs that block transport through the exocytic pathway, inhibit secretion of thioredoxin, indicating that the latter does not follow the classical ER-Golgi route. The secretory mechanism for thioredoxin shares several features with the alternative pathway described for interleukin-1 beta, such as the potentiating effect on secretion of several unrelated drugs and the sensitivity to methylamine. However, unlike interleukin-1 beta, thioredoxin is not detected in membrane-bound compartments of secreting cells. In addition, when COS7 are transfected with plasmids encoding pro-interleukin-1 beta or thioredoxin, only the latter is detectable extracellularly.