Wnt proteins regulate many developmental processes and are required for tissue homeostasis in adult animals. The cellular responses to Wnts are manifold and are determined by the respective Wnt ligand and its specific receptor complex in the plasma membrane. Wnt receptor complexes contain a member of the Frizzled family of serpentine receptors and a co-receptor, which commonly is a single-pass ...

Microglia, the immunocompetent cells of the central nervous system (CNS) and the brain’s own macrophages are the most motile cells in the CNS and those with highest plasticity, as they rapidly move their projections to actively screen their environment for any type of injury. Upon cell damage or infection, microglia respond quickly: they proliferate, change morphology from ramified to amoeboid ...

Ror receptor-tyrosine kinases act as Wnt-5a receptors in beta-catenin independent Wnt-signaling pathways. In Xenopus, expression of xPAPC is regulated by a Wnt-5a/Ror2 pathway, which resembles typical signaling cascades downstream of receptor-tyrosine kinases. Here, we have identified the phospho-tyrosine binding protein ShcA as an intracellular binding partner of Ror2. ShcA binds to a conserve...

Wnts regulate important intracellular signaling events, and dysregulation of the Wnt pathway has been linked to human disease. Here, we uncover numerous Wnt canonical effectors in human platelets where Wnts, their receptors, and downstream signaling components have not been previously described. We demonstrate that the Wnt3a ligand inhibits platelet adhesion, activation, dense granule secretion...

Wg/Wnts are paracrine and autocrine ligands that activate distinct signaling pathways while being internalized through surface receptors. Converging and contrasting views are shaping our understanding of whether, where, and how endocytosis may modulate Wnt signaling. We gather considerable amount of evidences to elaborate the point that signal-receiving cells utilize distinct, flexible, and sop...

R-spondin proteins are novel Wnt/β-catenin agonists, which signal through their receptors leucine-rich repeat-containing G-protein coupled receptor (LGR) 4/5/6 and substantially enhance Wnt/β-catenin activity. R-spondins are reported to function in embryonic development. They also play important roles in stem cell functions in adult tissues, such as the intestine and mammary glands, which large...

The morphology of the dendritic tree is critical to neuronal function and neural circuit wiring. Several Wnt family members have been demonstrated to play important roles in dendrite development. However, the Wnt receptors responsible for mediating this process remain largely elusive. Using primary hippocampal neuronal cultures as a model system, we report that Frizzled4 (Fzd4), a member of the...

Wnt signaling is mediated by three classes of receptors, Frizzled, Ryk, and Ror. In Caenorhabditis elegans, Wnt signaling regulates the anterior/posterior polarity of the P7.p vulval lineage, and mutations in lin-17/Frizzled cause loss or reversal of P7.p lineage polarity. We found that pak-1/Pak (p21-activated kinase), along with putative activators of Pak, nck-1/Nck, and ced-10/Rac, regulates...

Secreted proteins of the Wnt family affect axon guidance, asymmetric cell division, and cell fate. We show here that C. elegans Wnts acting through Frizzled receptors can shape axon and dendrite trajectories by reversing the anterior-posterior polarity of neurons. In lin-44/Wnt and lin-17/Frizzled mutants, the polarity of the PLM mechanosensory neuron is reversed along the body axis: the long P...

Mammalian LGR4, 5 and 6 are seven-transmembrane receptors that are important for diverse physiological processes. These receptors are orthologous to DLGR2, a Drosophila receptor activated by the burs/pburs heterodimer important for morphogenesis. Although recent studies indicated that four R-spondin proteins are cognate ligands for LGR4, 5 and 6 receptors, several BMP antagonists in vertebrates...