Beyond Wnt inhibition: new functions of secreted Frizzled-related proteins in development and disease
Author:
Bovolenta Paola12, Esteve Pilar12, Ruiz Jose Maria12, Cisneros Elsa12, Lopez-Rios Javier1
Affiliation:
1. Departamento de Neurobiología Molecular, Celular y del Desarrollo, Instituto Cajal, CSIC, Dr Arce 37, Madrid 28002, Spain 2. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Instituto de Salud Carlos III, Madrid, Spain
Abstract
The secreted Frizzled-related proteins (SFRPs) are a family of soluble proteins that are structurally related to Frizzled (Fz) proteins, the serpentine receptors that mediate the extensively used cell-cell communication pathway involving Wnt signalling. Because of their homology with the Wnt-binding domain on the Fz receptors, SFRPs were immediately characterised as antagonists that bind to Wnt proteins to prevent signal activation. Since these initial studies, interest in the family of SFRPs has grown progressively, offering new perspectives on their function and mechanism of action in both development and disease. These studies indicate that SFRPs are not merely Wnt-binding proteins, but can also antagonise one another's activity, bind to Fz receptors and influence axon guidance, interfere with BMP signalling by acting as proteinase inhibitors, and interact with other receptors or matrix molecules. Furthermore, their expression is altered in different types of cancers, bone pathologies, retinal degeneration and hypophosphatemic diseases, indicating that their activity is fundamental for tissue homeostasis. Here we review some of the debated aspects of SFRP-Wnt interactions and discuss the new and emerging roles of SFRPs.
Publisher
The Company of Biologists
Reference119 articles.
1. Adell, T., Thakur, A. N. and Muller, W. E. (2007). Isolation and characterization of Wnt pathway-related genes from Porifera. Cell Biol. Int.31, 939-949. 2. Armes, J. E., Hammet, F., de Silva, M., Ciciulla, J., Ramus, S. J., Soo, W. K., Mahoney, A., Yarovaya, N., Henderson, M. A., Gish, K. et al. (2004). Candidate tumor-suppressor genes on chromosome arm 8p in early-onset and high-grade breast cancers. Oncogene23, 5697-5702. 3. Bafico, A., Gazit, A., Pramila, T., Finch, P. W., Yaniv, A. and Aaronson, S. A. (1999). Interaction of frizzled related protein (FRP) with Wnt ligands and the frizzled receptor suggests alternative mechanisms for FRP inhibition of Wnt signaling. J. Biol. Chem.274, 16180-16187. 4. Banyai, L. and Patthy, L. (1999). The NTR module: domains of netrins, secreted frizzled related proteins, and type I procollagen C-proteinase enhancer protein are homologous with tissue inhibitors of metalloproteases. Protein Sci.8, 1636-1642. 5. Banziger, C., Soldini, D., Schutt, C., Zipperlen, P., Hausmann, G. and Basler, K. (2006). Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells. Cell125, 509-522.
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