How are Wnt signals transported from Wnt-producing cells to Wnt-responding cells?
The importance of communication in human communities has long been appreciated. It allows people to coordinate their actions and to assume specialized roles. Communication is also vital to “communities” of cells, such as tissues in multicellular organisms. Specifically, intercellular communication (also known as intercellular signaling) is critical for the proper regulation of cell specialization, proliferation, and migration. Dysregulation of intercellular signaling can lead to embryonic defects and diseases, including cancer.
Just as in humans, communication between two cells involves a cell that produces a signal (a “talking” cell) and a cell that responds to a signal (a “listening” cell). And just as the machinery involved in producing sound is distinct from that involved in hearing and responding to sound, the cellular machinery involved in producing a signal is distinct from that required for responding to a signal.
The Burrus lab is particularly interested in Wnt signaling proteins, which are critically important for embryogenesis and homeostasis. Disruption of Wnt signaling leads to developmental defects and diseases, such as cancer. The goal of our lab is to understand the molecular machinery involved in the production of Wnt proteins in “talking” cells as well as the transport of Wnt proteins to “listening” cells. So far, we understand that Wnts are translocated into the endoplasmic reticulum during translation. There, they undergo a critically important post-translational modification called palmitoylation. This modification anchors Wnt proteins the membrane bilayer. After palmitoylation, Wnts are carried to the surface by a cargo transporter (another protein) called Wntless (WLS).
For many years, it was presumed that Wnt signals spread from “talking” cells to “listening” cells by diffusion of secreted Wnt proteins away from the site of production. However, this model is not consistent with the observation that Wnts are anchored in the membrane bilayer. Recently, data from a number of labs, including our own, suggest a new model in which Wnts are transported to target cells via long filopodia. However, the role of these filopodia in both embryogenesis and oncogenesis remains poorly understood. The Burrus lab is currently using the techniques of cell, developmental and molecular biology as well as biochemistry to study the roles that filopodia play in Wnt signaling in vertebrate embryos and in triple negative breast cancer cells.