Apicobasal secretion of Wnt11 and Wnt3a in polarized epithelial cells is regulated by distinct mechanisms

• Published in: Journal of cell science
• Main Authors: Yamamoto, Hideki, Awada, Chihiro, Hanaki, Hideaki, Sakane, Hiroshi, Tsujimoto, Ikuko, Takahashi, Yuko, Takao, Toshifumi, Kikuchi, Akira
• Format: Journal Article
• Language: English
• Published: 01.01.2013
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.126052

Wnts are glycan- and lipid-modified morphogens that are important for cellular responses, but how Wnt is secreted in polarized epithelial cells remains unclear. Although Wntless (Wls) has been shown to interact with Wnts and support their secretion, the role of Wls in the sorting of Wnts to the final destination in polarized epithelial cells have not been clarified. Glycosylation was shown to be important for the sorting of some transmembrane and secreted proteins, but glycan profiles and their roles in the polarized secretion of Wnts are not known. Here we show the apicobasal secretion of Wnts is regulated by different mechanisms. Wnt11 and Wnt3a were secreted apically and basolaterally, respectively, in polarized epithelial cells. Wls was localized to the basolateral membrane. Mass-spectrometric analyses revealed that Wnt11 is modified with complex/hybrid-(Asn40), high-mannose-(Asn90), and high-mannose/hybrid-(Asn300) type glycans and that Wnt3a is modified with two high-mannose-type glycans (Asn87 and Asn298). Glycosylation processing at Asn40 and galectin-3 were required for the apical secretion of Wnt11, while clathrin and adaptor protein-1 were required for the basolateral secretion of Wnt3a. By the fusion of the Asn40 glycosylation site of Wnt11, Wnt3a was secreted apically. The recycling of Wls by AP-2 was necessary for the basolateral secretion of Wnt3a but not for the apical secretion of Wnt11. These results suggest that Wls has different roles on the polarized secretion of Wnt11 and Wnt3a and that glycosylation processing of Wnts decides their secretory routes.