Specific regulation of the adaptor protein complex AP-3 by the Arf GAP AGAP1
Specific regulation of the adaptor protein complex AP-3 by the Arf GAP AGAP1
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DOI：
10.1016/s1534-5807(03)00234-x
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发表时间：
2003-09-01
影响因子：
11.8
通讯作者：
Randazzo, PA
中科院分区：
文献类型：
--
作者：
Nie, ZZ;Boehm, M;Randazzo, PA
Arf 1通过与至少7种不同的囊泡外壳蛋白相互作用，在几个膜位点调节膜运输。在这里，我们测试的假设，Arf 1依赖外套是独立调节的特定相互作用与Arf GAP。我们发现，Arf GAP AGAP 1直接关联和共定位与AP-3，外壳蛋白复合物参与运输的内体-溶酶体系统。结合由AGAP 1的PH结构域和AP-3的δ和σ 3亚基介导。AGAP 1的过表达改变了AP-3的细胞分布，而AGAP 1的表达降低使AP-3对布雷菲德菌素A具有抗性。AGAP 1过表达不影响其他外壳蛋白的分布，AP-3分布不受其他Arf GAP过表达的影响。过表达AGAP 1的细胞也表现出增加的通过质膜的LAMP 1运输。综上所述，这些结果支持AGAP 1直接特异性调节AP-3依赖性贩运的假设。
Arf1 regulates membrane trafficking at several membrane sites by interacting with at least seven different vesicle coat proteins. Here, we test the hypothesis that Arf1-dependent coats are independently regulated by specific interaction with Arf GAPs. We find that the Arf GAP AGAP1 directly associates with and colocalizes with AP-3, a coat protein complex involved in trafficking in the endosomal-lysosomal system. Binding is mediated by the PH domain of AGAP1 and the delta and sigma3 subunits of AP-3. Overexpression of AGAP1 changes the cellular distribution of AP-3, and reduced expression of AGAP1 renders AP-3 resistant to brefeldin A. AGAP1 overexpression does not affect the distribution of other coat proteins, and AP-3 distribution is not affected by overexpression of other Arf GAPs. Cells overexpressing AGAP1 also exhibit increased LAMP1 trafficking via the plasma membrane. Taken together, these results support the hypothesis that AGAP1 directly and specifically regulates AP-3-dependent trafficking.