PPhosphatewas examined in GlcAT-I knockout embryos. Syntenin binds to syndecan and ALIX via the PDZ domain and N-terminal domain, respectively, and this tripartite complex is involved in the biogenesis of exosomes4). In addition, exosome formation requires cell membrane segregation as cytokinesis. In wild-type preimplantation embryos, syntenin was accumulated at the midbody during cytokinesis, whereas such accumulation was not observed in GlcAT-I knockout embryos. These results suggest that chondroitin sulfate chains are required for efficient scission during cytokinesis and exosome formation.XylGalGlcAGalNAcGlcNAcGalNAcT-II/GlcAT-IIGalNAcT-IIGalNAcT-IChGn-2ChGn-1EXT1/EXT2GlcNAcT-II/GlcAT-IIGlcNAcT-IIGlcNAcT-IEXTL1-Ser-SerSer-Ser2P-Ser2P-Ser2P-Ser-SerCS polymerase complexChSy1/ChSy2/ChSy3/ChPFHS polymerase complexEXTL3Core proteinXylTFam20BGalT-IGalT-IIPXYLPGlcAT-IFigure 1. Biosynthesis of chondroitin sulfate and heparan sulfateSeveral glycosyltransferases and distinct kinase/phosphatase(s) participate in the synthesis of the common tetrasaccharide linkage region and repeating disaccharide region characteristic of chondroitin sulfate (CS) and heparan sulfate (HS). XylT, xylosyltransferase; FAM20B, xylose 2-O-kinase; PXYLP, 2-O-phosphoxylose phosphatase; GalT-I, β1,4–galactosyltransferase-I; GalT-II, β1,3–galactosyltransferase-II; GlcAT-I, β1,3–glucuronyltransferase-I; EXT, exostosin; EXTL, EXT-like; ChSy, chondroitin synthase; ChPF, chondroitin polymerizing factor; ChGn, chondroitin GalNAc transferase. Transient Xyl phosphorylation of the tetrasaccharide linkage region by FAM20B and PXYLP contributes to the biosynthetic maturation of the linkage region, thus resulting in a sufficient supply of primers for glycosaminoglycan backbone synthesis by CS and HS polymerases.machinery. This spatiotemporal coordination of the abscission machinery is important for the completion of cytokinesis. To examine which step of cytokinesis might be impaired because of the lack of chondroitin sulfate, the expression of chondroitin sulfate was assessed by immunostaining. Chondroitin sulfate was enriched at the intercellular bridge and the midbody formed between two daughter cells at the last step of cell division. The disappearance of the signal after chondroitinase ABC treatment confirmed chondroitin sulfate localization. To further elucidate the molecular mechanism, the localization of various molecules involved in abscission, the last step of cytokinesis, References1) Kitagawa H. Using sugar remodeling to study chondroitin sulfate function. Biol. Pharm. Bull. (37): 1705-1712, 2014.2) Izumikawa T, Kanagawa N, Watamoto Y, Okada M, Saeki M, Sakano M, Sugahara K, Sugihara K, Asano M, Kitagawa H. Impairment of embryonic cell division and glycosaminoglycan biosynthesis in glucuronyltransferase-I-deficient mice. J. Biol. Chem. (285): 12190-12196, 2010.3) Izumikawa T, Sato B, Kitagawa H. Chondroitin sulfate is indispensable for pluripotency and differentiation of mouse embryonic stem cells. Sci. Rep. (4): 3701, 2014.4) Baietti, M. F., Zhang, Z., Mortier, E., Melchior, A., Degeest, G., Geeraerts, A., Ivarsson, Y., Depoortere, F., Coomans, C., Vermeiren, E., Zimmermann, P., and David, G. Syndecan-syntenin-ALIX regulates the biosynthesis of exosomes. Nat. Cell Biol. (14): 677-685, 2012.59
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