Open AccessMucin-type O-glycosylation controls pluripotency in mouse embryonic stem cells via Wnt receptor endocytosis
Author(s) -
Federico Pecori,
Yoshihiro Akimoto,
Hisatoshi Hanamatsu,
Yoshihiro Furukawa,
Yasuro Shinohara,
Yuzuru Ikehara,
Shoko Nishihara
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.245845
Subject(s) - biology , microbiology and biotechnology , glycosylation , wnt signaling pathway , endocytosis , embryonic stem cell , mucin , frizzled , signal transduction , receptor , biochemistry , gene
Mouse embryonic stem cells (ESCs) can differentiate into a range of cell types during development and this pluripotency is regulated by various extrinsic and intrinsic factors. Mucin-type O-glycosylation has been suggested to be a potential factor in the control of ESC pluripotency and is characterized by the addition of N-acetylgalactosamine (GalNAc) to serine or threonine residues of membrane-anchored proteins and secreted proteins. To date, the relationship between mucin-type O-glycosylation and signaling in ESCs remains undefined. Here, we identify the elongation pathway via C1GalT1 that synthesizes T antigen (Galβ1-3GalNAc) as the most prominent among mucin-type O-glycosylation modifications in ESCs. Moreover, we show that mucin-type O-glycosylation on the Wnt signaling receptor Frizzled-5 regulates its endocytosis via galectin-3 binding to T antigen, and that reduction of T antigen results in the exit of the ESCs from pluripotency via canonical Wnt signaling activation. Our findings reveal a novel regulatory mechanism that modulates Wnt signaling and, consequently, ESC pluripotency.