Golgi Phosphoprotein 3 Mediates the Golgi Localization and Function of Protein O-Linked Mannose β-1,2-N-Acetlyglucosaminyltransferase 1
Golgi Phosphoprotein 3 Mediates the Golgi Localization and Function of Protein O-Linked Mannose β-1,2-N-Acetlyglucosaminyltransferase 1
复制标题
DOI：
10.1074/jbc.m114.548305
复制
发表时间：
2014-05-23
影响因子：
4.8
通讯作者：
Song, Zhiwei
中科院分区：
文献类型：
--
作者：
Pereira, Natasha A.;Pu, Helen X.;Song, Zhiwei
GOLPH3是一种在真核生物谱系中发现的高度保守蛋白。酵母同源物Vps74p与几种甘露糖基转移酶相互作用并维持高尔基定位，这对酵母的N和o糖基化至关重要。通过使用T7噬菌体展示，我们发现了GOLPH3和哺乳动物糖基转移酶POMGnT1之间的一种新的相互作用，这种相互作用参与了α -三磷酸甘聚糖的o -甘露糖基化。POMGnT1的细胞质尾部在介导其与GOLPH3的相互作用中起关键作用。这种相互作用的缺失导致POMGnT1无法定位到高尔基体，并降低了α -歧义聚糖的功能性糖基化。此外，我们发现POMGnT1茎结构域中存在三个临床相关突变，错误定位到内质网，这突出了确定糖基转移酶高尔基定位的分子机制的重要性。我们的研究结果揭示了GOLPH3在介导POMGnT1高尔基体定位中的新作用。
GOLPH3 is a highly conserved protein found across the eukaryotic lineage. The yeast homolog, Vps74p, interacts with and maintains the Golgi localization of several mannosyltransferases, which is subsequently critical for N- and O-glycosylation in yeast. Through the use of a T7 phage display, we discovered a novel interaction between GOLPH3 and a mammalian glycosyltransferase, POMGnT1, which is involved in the O-mannosylation of alpha-dystroglycan. The cytoplasmic tail of POMGnT1 was found to be critical for mediating its interaction with GOLPH3. Loss of this interaction resulted in the inability of POMGnT1 to localize to the Golgi and reduced the functional glycosylation of alpha-dystroglycan. In addition, we showed that three clinically relevant mutations present in the stem domain of POMGnT1 mislocalized to the endoplasmic reticulum, high-lighting the importance of identifying the molecular mechanisms responsible for Golgi localization of glycosyltransferases. Our findings reveal a novel role for GOLPH3 in mediating the Golgi localization of POMGnT1.