We have found that components of the Wnt signaling pathways are expressed in erythrocytes and that these cells respond to the Wnt ligands.

We show that the Wnt ligands modulate the erythrocyte cytoskeleton, enabling its flexibility and strength. Furthermore, Wnts prolong erythrocyte survival both ex-vivo, under storage conditions, and in post-transfusion recipient mice. We also demonstrate that a Wnt ligand is secreted into the plasma and that monocytes and lymphocytes express and most likely secrete the Wnt effectors into the circulation.

These findings provide evidence for intracellular signaling activity in enucleated cells and open new avenues for studying the function of signaling pathways in the bloodstream.