Golgi Phosphoprotein 3 Triggers Signal-mediated Incorporation of Glycosyltransferases into Coatomer-coated (COPI) Vesicles
Golgi Phosphoprotein 3 Triggers Signal-mediated Incorporation of Glycosyltransferases into Coatomer-coated (COPI) Vesicles
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DOI：
10.1074/jbc.m114.608182
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发表时间：
2014-11-07
影响因子：
4.8
通讯作者：
Popoff, Vincent
中科院分区：
文献类型：
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作者：
Eckert, Elias S. P.;Reckmann, Ingeborg;Popoff, Vincent
新合成的膜和分泌蛋白在高尔基体中经历一系列翻译后修饰，包括碳水化合物部分的附着。如此形成的聚糖的最终结构由不同糖基化步骤的执行顺序决定，这似乎与高尔基体内糖基转移酶和糖基水解酶的空间分布密切相关。细胞如何实现这些酶的准确定位尚不完全清楚，但可能涉及动态过程，例如涂层异构体包被（COPI）囊泡介导的运输。在酵母中，这种转运可能受到液泡蛋白分选 74 (Vps74p) 的调节，液泡蛋白分选 74 (Vps74p) 是一种外周高尔基体蛋白，能够与 COPI 外壳以及某些甘露糖基转移酶胞质尾部中存在的结合基序相互作用。最近，Vps74 的哺乳动物同源物高尔基体磷蛋白 3 (GOLPH3) 已被证明可以控制核心 2 N-乙酰葡萄糖胺转移酶 1 的高尔基体定位。在这里，我们强调 GOLPH3 在 α-2,6-唾液酸转移酶 1 的空间定位中的作用。我们首次表明，GOLPH3 支持两个核心的掺入2N-乙酰氨基葡萄糖转移酶 1 和 α-2,6-唾液酸转移酶 1 进入 COPI 囊泡。 GOLPH3 的耗尽改变了这些酶的亚细胞定位。相反，半乳糖基转移酶（一种不与 GOLPH3 相互作用的酶）既不整合到 COPI 囊泡中，也不依赖于 GOLPH3 进行正确定位。
Newly synthesized membrane and secreted proteins undergo a series of posttranslational modifications in the Golgi apparatus, including attachment of carbohydrate moieties. The final structure of so-formed glycans is determined by the order of execution of the different glycosylation steps, which seems intimately related to the spatial distribution of glycosyltransferases and glycosyl hydrolases within the Golgi apparatus. How cells achieve an accurate localization of these enzymes is not completely understood but might involve dynamic processes such as coatomer-coated (COPI) vesicle-mediated trafficking. In yeast, this transport is likely to be regulated by vacuolar protein sorting 74 (Vps74p), a peripheral Golgi protein able to interact with COPI coat as well as with a binding motif present in the cytosolic tails of some mannosyltransferases. Recently, Golgi phosphoprotein 3 (GOLPH3), the mammalian homolog of Vps74, has been shown to control the Golgi localization of core 2 N-acetyl-glucosamine- transferase 1. Here, we highlight a role of GOLPH3 in the spatial localization of alpha-2,6-sialyltransferase 1. We show, for the first time, that GOLPH3 supports incorporation of both core 2N-acetylglucosamine-transferase 1 and alpha-2,6-sialyltransferase 1 into COPI vesicles. Depletion of GOLPH3 altered the subcellular localization of these enzymes. In contrast, galactosyltransferase, an enzyme that does not interact with GOLPH3, was neither incorporated into COPI vesicles nor was dependent on GOLPH3 for proper localization.