title: β4GalT6 is involved in the synthesis of lactosylceramide with less intensity than β4GalT5.
abstract: Glycosphingolipids are expressed on the cell membrane and act as important factors in various events that occur across the plasma membrane. Lactosylceramide (LacCer) is synthesized from glucosylceramide and is a common precursor of various glycosphingolipids existing in whole body. Based on the enzyme purification, β1,4-galactosyltransferase 6 (B4galt6) cDNA was isolated as a LacCer synthase-coding gene in the rat brain. We generated B4galt6 gene knockout (KO) mice and analyzed their phenotypes to examine roles of β4GalT6. B4galt6 KO mice were born and grew up apparently normal. LacCer synthase activity and the composition of acidic glycosphingolipids in the brain were almost equivalent or minimally different between wild-type and KO mice. Studies by mouse embryonic fibroblasts (MEFs) revealed that the silencing of B4galt5 gene resulted in the marked reduction in LacCer synthase activity and this reduction was more severe in MEFs derived from B4galt6 KO mice than those from wild-type mice. These results suggested that β4GalT6 plays a role as a LacCer synthase, whereas β4GalT5 acts as a main enzyme for LacCer biosynthesis in these tissues and cells.
authors.affiliation: Department of Biochemistry II.
authors.forename: Noriyo
authors.initials: N
authors.lastname: Tokuda
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Numata
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Li
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nomura
authors.forename: Minoru
authors.initials: M
authors.lastname: Takizawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kondo
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Noboru
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Tohru
authors.initials: T
authors.lastname: Kiyono
authors.forename: Takeshi
authors.initials: T
authors.lastname: Urano
authors.forename: Keiko
authors.initials: K
authors.lastname: Furukawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism*; D007790:Lactosylceramides / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype
chemical_list: D007790:Lactosylceramides; C587194:B4galt6 protein, mouse; D005700:Galactosyltransferases
keywords: glycosphingolipid; kidney; knockout; lactosylceramide; β4-galactosyltransferase