Wnt family proteins are secreted and associated with the cell surface.

Abstract

Members of the Wnt gene family are proposed to function in both normal development and differentiation as well as in mammary tumorigenesis. To understand the function of Wnt proteins in these two processes, we present here a biochemical characterization of seven Wnt family members. For these studies, AtT-20 cells, a neuroendocrine cell line previously shown to efficiently process and secrete Wnt-1, was transfected with expression vectors encoding Wnt family members. All of the newly characterized Wnt proteins are glycosylated, secreted proteins that are tightly associated with the cell surface or extracellular matrix. We have also identified native Wnt proteins in retinoic acid-treated P19 embryonal carcinoma cells, and they exhibit the same biochemical characteristics as the recombinant proteins. These data suggest that Wnt family members function in cell to cell signaling in a fashion similar to Wnt-1.

Controlled levels of canonical Wnt signaling are required for neural crest migration

“…Signaling through some Wnts such as; Wnt1 (Hinck et al, 1994;Young et al, 1998;Shimizu et al, 1997), Wnt3a (Shimizu et al, 1997) and Wnt8 (Wikramanayake et al, 2004;Kohn and Moon, 2005) has been shown to correlate with accumulation of β-catenin in the nucleus and transcriptional changes, while signaling trough others like Wnt5a (Shimizu et al, 1997;Kikuchi et al, 2012) and Wnt11 (Kohn and Moon, 2005;Tada and Smith, 2000;Pandur et al, 2002) is β-catenin-independent and involves regulation of cytoskeleton or calcium release. All the metazoan species express Wnt genes and all of those genes encode secreted proteins based on their amino acid structure and biochemical characterization (Coudreuse and Korswagen, 2007;Smolich et al, 1993). Upon translation and targeting to the extracellular space, Wnt proteins are exposed to various modifications, which are essential for folding, secretion and Wnt-signaling activity (Mikels and Nusse, 2006;Coudreuse and Korswagen, 2007;Willert and Nusse, 2012).…”

Wnt Signaling from Development to Disease: Insights from Model Systems

“…Cadigan and M. Peifer transported through the endomembrane system to the cell surface and undergo several modifications. Wnts undergo N-linked glycosylation (Burrus and McMahon 1995;Kadowaki et al 1996;Komekado et al 2007;Kurayoshi et al 2007;Mason et al 1992;Smolich et al 1993;Tanaka et al 2002). Several Wnts also are palmitoylated at the first conserved cysteine (Galli et al 2007;Kadowaki et al 1996;Komekado et al 2007;Willert et al 2003).…”

Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling

“…A series of experiments using tunicamycin have shown that Wnt-5a is modified with asparagine-linked glycans [29]. However, which amino acids are modified has not been determined.…”