Targeting of the Arf-GEF GBF1 to lipid droplets and Golgi membranes
Targeting of the Arf-GEF GBF1 to lipid droplets and Golgi membranes
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DOI：
10.1242/jcs.134254
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发表时间：
2013-10-15
影响因子：
4
通讯作者：
Jackson, Catherine L.
中科院分区：
文献类型：
--
作者：
Bouvet, Samuel;Golinelli-Cohen, Marie-Pierre;Jackson, Catherine L.
脂滴代谢和分泌途径运输都需要激活Arf 1小G蛋白。Arf 1激活的时空调节是由GBF和BIG家族的鸟嘌呤核苷酸交换因子（GEF）介导的，但其定位于细胞内多个位点的机制知之甚少。在这里，我们表明，GBF 1有一个脂质结合结构域（HDS 1）的催化Sec 7结构域的下游，介导协会与细胞中的脂滴和高尔基体膜，并与双层脂质体和人工液滴在体外。HDS 1内的两亲性螺旋对于体外和细胞中的脂质结合是必要的和足够的。GBF 1的HDS 1结构域与细胞中的脂滴稳定相关，并且催化Sec 7结构域抑制这种有效的脂滴结合能力。Sec 7结构域-HDS 1串联体上游的额外序列是定位于高尔基体膜所必需的。这种机制提供了深入了解之间的串扰脂滴功能和分泌贩运。
Lipid droplet metabolism and secretory pathway trafficking both require activation of the Arf1 small G protein. The spatiotemporal regulation of Arf1 activation is mediated by guanine nucleotide exchange factors (GEFs) of the GBF and BIG families, but the mechanisms of their localization to multiple sites within cells are poorly understood. Here we show that GBF1 has a lipid-binding domain (HDS1) immediately downstream of the catalytic Sec7 domain, which mediates association with both lipid droplets and Golgi membranes in cells, and with bilayer liposomes and artificial droplets in vitro. An amphipathic helix within HDS1 is necessary and sufficient for lipid binding, both in vitro and in cells. The HDS1 domain of GBF1 is stably associated with lipid droplets in cells, and the catalytic Sec7 domain inhibits this potent lipid-droplet-binding capacity. Additional sequences upstream of the Sec7 domain-HDS1 tandem are required for localization to Golgi membranes. This mechanism provides insight into crosstalk between lipid droplet function and secretory trafficking.