WLS Human

Wntless was initially identified through genetic studies in Drosophila and C. elegans, where it was found to be essential for the secretion of Wnt proteins . The protein is known by several names, reflecting its discovery in different organisms and contexts. In humans, it is commonly referred to as Wntless or WLS.

Wntless is a multiple-pass transmembrane protein that resides in the endoplasmic reticulum (ER) and Golgi apparatus . It binds to Wnt proteins within the cell and facilitates their transport to the cell surface, where they can be secreted into the extracellular environment. This process is critical for the activation of Wnt signaling pathways in target cells.

The Wnt signaling pathway is highly conserved across multicellular animals and is involved in numerous biological processes. It plays a crucial role in early embryonic development, tissue homeostasis, and stem cell renewal . Dysregulation of Wnt signaling has been implicated in various diseases, including cancer, making Wntless a protein of significant interest in biomedical research.

Recent studies have provided detailed insights into the structure and function of Wntless. For instance, a study published in Nature Communications reported the cryo-EM structure of human Wntless in complex with Wnt3a at a resolution of 2.2 Å . This high-resolution structure revealed three major binding regions between Wntless and Wnt3a, which are crucial for their interaction and the subsequent secretion of Wnt3a .

Understanding the molecular mechanisms of Wntless-mediated Wnt secretion has significant therapeutic implications. The high-resolution structure of the Wntless-Wnt3a complex provides valuable insights for the development of targeted therapies for diseases associated with aberrant Wnt signaling, such as cancer .