Abstract
N-linked carbohydrate modification is found in many secretary and cell surface proteins. This post-translational modification is thought to be important for biological function of proteins in vivo. Recent gene knockout studies demonstrated biological function of glycoproteins, and revealed as yet unknown biosynthetic pathway of N-glycans. We have analyzed the functions of α-mannosidase II (MII) and α-mannosidase IIx (MX) in the mouse by targeted disruption of each gene, and demonstrated that enzymatic activity of either MII or MX enzymes is essential for N-glycan biosynthesis in vivo. Mutant mice lacking both enzymatic activities die shortly after birth owing to respiration failure, thus suggesting the essential role of complex-type N-glycan in the lung of neonates.
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References
Akama TO, Nakagawa H, Sugihara K, Narisawa S, Ohyama C, Nishimura S, O’Brien DA, Moremen KW, Millan JL, Fukuda MN (2001) Germ cell survival through carbohydrate-mediated interaction with Sertoli cells. Science 295:124–127
Akama TO, Nakagawa H, Wong NK, Sutton-Smith M, Dell A, Morris HR, Nakayama J, Nishimura S, Pai A, Moremen KW, Marth JD, Fukuda MN (2006) Essential and mutually compensatory roles of alpha-mannosidase II and alpha-mannosidase IIx in N-glycan processing in vivo in mice. Proc Natl Acad Sci USA 103:8983–8988
Chui D, Oh-Eda M, Liao YF, Panneerselvam K, Lal A, Marek KW, Freeze HH, Moremen KW, Fukuda MN, Marth JD (1997) Alpha-mannosidase-II deficiency results in dyserythropoiesis and unveils an alternate pathway in oligosaccharide biosynthesis. Cell 90:157–167
Chui D, Sellakumar G, Green RS, Sutton-Smith M, McQuistan T, Marek KW, Morris HR, Dell A, Marth JD (2001) Genetic remodeling of protein glycosylation in vivo induces autoimmune disease. Proc Natl Acad Sci USA 98:1142–1147
Ioffe E, Stanley P (1994) Mice lacking N-acetylglucosaminyltransferase I activity die at mid-gestation, revealing an essential role for complex or hybrid N-linked carbohydrates. Proc Natl Acad Sci USA 91:728–732
Metzler M, Gertz A, Sarkar M, Schachter H, Schrader JW, Marth JD (1994) Complex asparagine-linked oligosaccharides are required for morphogenic events during post-implantation development. EMBO J 13:2056–2065
Misago M, Liao YF, Kudo S, Eto S, Mattei MG, Moremen KW, Fukuda MN (1995) Molecular cloning and expression of cDNAs encoding human alpha-mannosidase II and a previously unrecognized alpha-mannosidase IIx isozyme. Proc Natl Acad Sci USA 92:11766–11770
Wang Y, Tan J, Sutton-Smith M, Ditto D, Panico M, Campbell RM, Varki NM, Long JM, Jaeken J, Levinson SR, Wynshaw-Boris A, Morris HR, Le D, Dell A, Schachter H, Marth JD (2001) Modeling human congenital disorder of glycosylation type IIa in the mouse: conservation of asparagine-linked glycan-dependent functions in mammalian physiology and insights into disease pathogenesis. Glycobiology 11:1051–1070
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Akama, T.O., Fukuda, M.N. (2008). Processing Enzymes Involved in N-glycan Biosynthesis and Related Genes: the Golgi N-glycan Processing α-mannosidase II and α-mannosidase IIx. In: Taniguchi, N., Suzuki, A., Ito, Y., Narimatsu, H., Kawasaki, T., Hase, S. (eds) Experimental Glycoscience. Springer, Tokyo. https://doi.org/10.1007/978-4-431-77922-3_27
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DOI: https://doi.org/10.1007/978-4-431-77922-3_27
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-77921-6
Online ISBN: 978-4-431-77922-3
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