DRAM1 deficiency affects the organization and function of the Golgi apparatus
DRAM1 deficiency affects the organization and function of the Golgi apparatus
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DRAM1 缺陷会影响高尔基体的组织和功能
DOI：
10.1016/j.cellsig.2019.109375
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发表时间：
2019
影响因子：
4.8
通讯作者：
Qin Zheng Hong
中科院分区：
文献类型：
--
作者：
Wei Mingzhen;Zhu Zhou;Wu Junchao;Wang Yan;Geng Ji;Qin Zheng Hong
DRAM1(DNA损伤调节自噬调节器1)是一种跨膜蛋白，主要定位于溶酶体，但也存在于其他膜细胞器中；然而，它在这些细胞器中的功能在很大程度上仍不清楚。我们发现DRAM1部分位于高尔基体中，并且DRAM1的敲除会导致细胞中高尔基体的碎裂。高尔基体碎裂现象与微管结构无关，DRAM1与高尔基体结构蛋白(ARF1、GM130、Synaxin 6、GRASP55)之间没有直接相互作用。此外，针对高尔基体的DRAM1未能挽救DRAM1缺陷细胞中高尔基体的碎裂。在DRAM1基因敲除细胞中，TS045-VSVG-GFP的转运被延迟。TS045-VSVG-GFP是高尔基体向质膜运动的指示剂。此外，在DRAM1基因敲除细胞中，CI-MPR从质膜到高尔基体的转运也受到阻碍。这些结果表明，DRAM1调节高尔基体的结构，并影响高尔基体相关的囊泡运输。
DRAM1 (DNA damage-regulated autophagy modulator 1) is a transmembrane protein that predominantly localizes to the lysosome but is also found in other membranous organelles; however, its function in these organelles remains largely unknown. We found that DRAM1 was partially located in the Golgi apparatus, and knockdown of DRAM1 caused fragmentation of the Golgi apparatus in cells. The phenomenon of fragmented Golgi was not related to microtubule organization, and there was no direct interaction between DRAM1 and Golgi structural proteins (ARF1, GM130, syntaxin 6 and GRASP55). Moreover, Golgi-targeting DRAM1 failed to rescue the fragmentation of Golgi in DRAM1-deficient cells. The transport of ts045-VSVG-GFP, an indicator of movement from the Golgi apparatus to the plasma membrane, was delayed in DRAM1-knockdown cells. Moreover, the trafficking of CI-MPR from the plasma membrane to the Golgi was also impeded in DRAM1-knockdown cells. These results indicated that DRAM1 regulated the structure of the Golgi apparatus and affected Golgi apparatus-associated vesicular transport.