Lipocalin 24p3 is regulated by the Wnt pathway independent of regulation by iron

Lipocalin 24p3 plays a direct role in iron transport and regulates the levels of important proteins of the iron metabolism. Iron-loaded 24p3 binds to its specific receptor (24p3R) on the cell surface. Upon binding to its receptor, 24p3 is internalized into the cell, where it releases its bound iron. Iron-free 24p3 can withdraw iron from inside the cell to the outside by a reverse mechanism. We analyzed the role of the murine 24p3 gene Lcn2 (alias 24p3) as a target of the Wnt pathway. In cells with activated Wnt pathway, the levels of 24p3 protein and RNA were decreased. The withdrawal of iron led to 24p3 downregulation, and iron addition to iron-deprived cells induced 24p3 expression. Despite its strong inhibitory effect on 24p3 expression, Wnt pathway activation had no effect on the intracellular iron level. In cells with nonactivated Wnt pathway, we found an as yet unidentified transcript of 24p3R. Our results indicate independent regulation of 24p3 expression by the Wnt pathway and by the intracellular iron level. Differential splicing of the 24p3R transcript, depending on the activation state of the Wnt pathway, may modify the function of 24p3.