Recycling of Golgi glycosyltransferases requires direct binding to coatomer
Recycling of Golgi glycosyltransferases requires direct binding to coatomer
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DOI：
10.1073/pnas.1810291115
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发表时间：
2018-09-04
影响因子：
11.1
通讯作者：
Kornfeld, Stuart
中科院分区：
文献类型：
--
作者：
Liu, Lin;Doray, Balraj;Kornfeld, Stuart
哺乳动物高尔基复合体的糖基转移酶必须在该细胞器的堆叠池之间循环，以维持其适当的稳态定位。这种运输是由COPI包被的囊泡介导的，但是糖基转移酶如何被整合到这些运输囊泡中还知之甚少。在这里，我们表明，N-末端胞质尾（N-尾巴）的顺式高尔基体糖基转移酶，共享一个phi-（K/R）-X-L-X-（K/R）序列直接结合到δ和ζ亚基的COPI。该N-尾基序的突变损害与COPI亚基的结合，导致转移酶错误定位于溶酶体。这些相互作用的生理学重要性通过粘脂沉积症III患者的GlcNAc-1-磷酸转移酶的N-尾中具有错义突变来说明，所述错义突变导致转移酶在溶酶体中快速降解。这些研究表明，哺乳动物顺式高尔基体糖基转移酶的N-尾与COPI亚基的直接结合对于高尔基体内的再循环至关重要。
The glycosyltransferases of the mammalian Golgi complex must recycle between the stacked cisternae of that organelle to maintain their proper steady-state localization. This trafficking is mediated by COPI-coated vesicles, but how the glycosyltransferases are incorporated into these transport vesicles is poorly understood. Here we show that the N-terminal cytoplasmic tails (N-tails) of a number of cis Golgi glycosyltransferases which share a phi-(K/R)-X-L-X-(K/R) sequence bind directly to the delta- and zeta-subunits of COPI. Mutations of this N-tail motif impair binding to the COPI subunits, leading to mislocalization of the transferases to lysosomes. The physiological importance of these interactions is illustrated by mucolipidosis III patients with missense mutations in the N-tail of GlcNAc-1-phosphotransferase that cause the transferase to be rapidly degraded in lysosomes. These studies establish that direct binding of the N-tails of mammalian cis Golgi glycosyltransferases with COPI subunits is essential for recycling within the Golgi.