Premium
PIG‐M transfers the first mannose to glycosylphosphatidylinositol on the lumenal side of the ER
Author(s) -
Maeda Yusuke,
Watanabe Reika,
Harris Claire L.,
Hong Yeongjin,
Ohishi Kazuhito,
Kinoshita Keiko,
Kinoshita Taroh
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.1.250
Subject(s) - biology , endoplasmic reticulum , mannose , biosynthesis , biochemistry , transmembrane protein , transmembrane domain , membrane protein , microbiology and biotechnology , membrane topology , amino acid , gene , membrane , receptor
Glycosylphosphatidylinositol (GPI) acts as a membrane anchor of many cell surface proteins. Its structure and biosynthetic pathway are generally conserved among eukaryotic organisms, with a number of differences. In particular, mammalian and protozoan mannosyltransferases needed for addition of the first mannose (GPI‐MT‐I) have different substrate specificities and are targets of species‐ specific inhibitors of GPI biosynthesis. GPI‐MT‐I, however, has not been molecularly characterized. Characterization of GPI‐MT‐I would also help to clarify the topology of GPI biosynthesis. Here, we report a human cell line defective in GPI‐MT‐I and the gene responsible, PIG‐M. PIG‐M encodes a new type of mannosyltransferase of 423 amino acids, bearing multiple transmembrane domains. PIG‐M has a functionally important DXD motif, a characteristic of many glycosyltransferases, within a domain facing the lumen of the endoplasmic reticulum (ER), indicating that transfer of the first mannose to GPI occurs on the lumenal side of the ER membrane.