The human thioredoxin reductase-1 splice variant TXNRD1_v3 is an atypical inducer of cytoplasmic filaments and cell membrane filopodia

Thioredoxin reductases are important selenoproteins maintaining cellular redox balance and regulating several redox dependent processes in apoptosis, cell proliferation and differentiation. Specific functions of dedicated splice variants may add further complexity to the functions of these proteins. We show here that a splice variant of human thioredoxin reductase 1, TXNRD1_v3, forms both dynamic cytoplasmic filaments and provokes instantaneous formation of dynamic cell membrane protrusions identified as filopodia. Using truncated versions of the protein we found that both the cytoplasmic filaments and the filopodia formation were exclusively dependent on the glutaredoxin domain of the protein. Interestingly, actin polymerization was required for filopodia formation triggered by TXNRD1_v3, but not for generation of cytoplasmic filaments. We conclude that the glutaredoxin domain of TXNRD1_v3 is an atypical regulator of the cell cytoskeleton that potently induces formation of highly ordered cytoplasmic filaments and cell membrane filopodia.