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Initial enzyme for glycosylphosphatidylinositol biosynthesis requires PIG‐P and is regulated by DPM2
Author(s) -
Watanabe Reika,
Murakami Yoshiko,
Marmor Mina D.,
Inoue Norimitsu,
Maeda Yusuke,
Hino Jun,
Kangawa Kenji,
Julius Michael,
Kinoshita Taroh
Publication year - 2000
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/19.16.4402
Subject(s) - biology , dolichol , biosynthesis , mannose , glycosyltransferase , biochemistry , atp synthase , enzyme , mutant , glycoprotein , gene
Glycosylphosphatidylinositols (GPIs) are attached to the C‐termini of many proteins, thereby acting as membrane anchors. Biosynthesis of GPI is initiated by GPI‐ N ‐acetylglucosaminyltransferase (GPI‐GnT), which transfers N ‐acetylglucosamine from UDP‐ N ‐acetylglucosamine to phosphatidylinositol. GPI‐GnT is a uniquely complex glycosyltransferase, consisting of at least four proteins, PIG‐A, PIG‐H, PIG‐C and GPI1. Here, we report that GPI‐GnT requires another component, termed PIG‐P, and that DPM2, which regulates dolichol‐phosphate‐mannose synthase, also regulates GPI‐GnT. PIG‐P, a 134‐amino acid protein having two hydrophobic domains, associates with PIG‐A and GPI1. PIG‐P is essential for GPI‐GnT since a cell lacking PIG‐P is GPI‐anchor negative. DPM2, but not two other components of dolichol‐phosphate‐mannose synthase, associates with GPI‐GnT through interactions with PIG‐A, PIG‐C and GPI1. Lec15 cell, a null mutant of DPM2, synthesizes early GPI intermediates, indicating that DPM2 is not essential for GPI‐GnT; however, the enzyme activity is enhanced 3‐fold in the presence of DPM2. These results reveal new essential and regulatory components of GPI‐GnT and imply co‐regulation of GPI‐GnT and the dolichol‐phosphate‐mannose synthase that generates a mannosyl donor for GPI.