Wnt signalling and endocytosis: Mechanisms, controversies and implications for stress responses

Abstract

Wnt signalling is one of a few conserved pathways that control diverse aspects of development and morphogenesis in all metazoan species. Endocytosis is a key mechanism that regulates the secretion and graded extracellular distribution of Wnt glycoproteins from the source cells, as well as Wnt signal transduction in the receiving cells. However, controversies exist regarding the requirement of clathrin-dependent endocytosis in Wnt signalling. Various lines of evidence from recent studies suggest that Wnt-β-catenin signalling is also involved in the regulation of cellular stress responses in adulthood, a role that is beyond its canonical functions in animal development. In this review, we summarise recent advances in the molecular and cellular mechanisms by which endocytosis modulates Wnt signalling. We also discuss how Wnt signalling could be repurposed to regulate mitochondrial stress response in the nematode Caenorhabditis elegans.