Abstract
Wnt signaling pathways constitute a group of signal transduction pathways that direct many physiological processes, such as development, growth, and differentiation. Dysregulation of these pathways is thus associated with many pathological processes, including neurodegenerative diseases, metabolic disorders, and cancer. At the same time, alterations are observed in plasma membrane compositions, lipid organizations, and ordered membrane domains in brain and metabolic diseases that are associated with Wnt signaling pathway activation. Here, we discuss the relationships between plasma membrane components—specifically ligands, (co) receptors, and extracellular or membrane-associated modulators—to activate Wnt pathways in several brain and metabolic diseases. Thus, the Wnt–receptor complex can be targeted based on the composition and organization of the plasma membrane, in order to develop effective targeted therapy drugs.
Highlights
Wnt signaling pathways are highly conserved in the animal kingdom, based on their components and functional roles in the regulation of development, tissue homeostasis, and regeneration [1,2,3,4,5,6,7,8]
The Wnt signaling pathways are essential for many cellular events that take place in development, homeostasis, and regeneration
Being the initiator of Wnt–receptor complex formation that activates the signaling pathway, the plasma membrane plays an essential role in the regulation of Wnt signaling
Summary
Wnt signaling pathways are highly conserved in the animal kingdom, based on their components and functional roles in the regulation of development, tissue homeostasis, and regeneration [1,2,3,4,5,6,7,8]. The plasma membrane consists of nanodomains—the so-called ordered membrane domains or lipid rafts that are defined as dynamic assemblies of various saturated lipids, sterols, glycosphingolipids, and glycosyl-phosphatidylinositol (GPI)-anchored proteins [12,13,14]. These domains influence membrane fluidity and receptor trafficking, thereby playing a key role in the functioning of receptors, protein sorting, and regulation of receptor-mediated signaling [15,16,17,18].
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