RNAi screen identifies a role for adaptor protein AP-3 in sorting to the regulated secretory pathway.
RNAi screen identifies a role for adaptor protein AP-3 in sorting to the regulated secretory pathway.
复制标题
DOI：
10.1083/jcb.201006131
复制
发表时间：
2010-12-13
期刊：
影响因子：
--
通讯作者：
Edwards RH
中科院分区：
文献类型：
--
作者：
Asensio CS;Sirkis DW;Edwards RH
AP-3将蛋白质浓缩在大的致密核心囊泡中，以促进受调节的胞吐作用。蛋白质的调节释放取决于它们包含在能够调节胞吐作用的大致密核心囊泡（LDCV）内。LDCV在trans-Golgi网络（TGN）形成，但蛋白质分选到该调节分泌途径（RSP）的机制以及参与该过程的胞质机器仍然知之甚少。我们现在在黑腹果蝇S2细胞中使用RNA干扰筛选，鉴定了少量基因，包括异四聚体衔接蛋白AP-3的几个亚基，这些基因是分选RSP所需的。在哺乳动物神经内分泌细胞中，由于LDCV形成中的主要缺陷，AP-3的缺失使胞吐失调。以前的工作涉及AP-3的内吞途径，但我们发现，AP-3促进分选的RSP内的生物合成途径在TGN的水平。虽然囊泡与致密的核心仍然形成在AP-3的情况下，它们包含显着较少的synaptotagmin 1，表明AP-3集中所需的蛋白质调节胞吐。
AP-3 concentrates proteins within large dense-core vesicles to promote regulated exocytosis. The regulated release of proteins depends on their inclusion within large dense-core vesicles (LDCVs) capable of regulated exocytosis. LDCVs form at the trans-Golgi network (TGN), but the mechanism for protein sorting to this regulated secretory pathway (RSP) and the cytosolic machinery involved in this process have remained poorly understood. Using an RNA interference screen in Drosophila melanogaster S2 cells, we now identify a small number of genes, including several subunits of the heterotetrameric adaptor protein AP-3, which are required for sorting to the RSP. In mammalian neuroendocrine cells, loss of AP-3 dysregulates exocytosis due to a primary defect in LDCV formation. Previous work implicated AP-3 in the endocytic pathway, but we find that AP-3 promotes sorting to the RSP within the biosynthetic pathway at the level of the TGN. Although vesicles with a dense core still form in the absence of AP-3, they contain substantially less synaptotagmin 1, indicating that AP-3 concentrates the proteins required for regulated exocytosis.
登录
查看更多内容
影响因子：
9.8
作者：
Devos D;Dokudovskaya S;Alber F;Williams R;Chait BT;Sali A;Rout MP
通讯作者：
Rout MP
DOI：
10.1073/pnas.0509844103
发表时间：
2006-06-27
影响因子：
11.1
作者：
Grabner, Chad P.;Price, Steven D.;Fox, Aaron P.
通讯作者：
Fox, Aaron P.
影响因子：
16.2
作者：
Berwin, B;Floor, E;Martin, TFJ
通讯作者：
Martin, TFJ
影响因子：
64.5
作者：
Cool, DR;Normant, E;Loh, YP
通讯作者：
Loh, YP
影响因子：
64.8
作者：
Bard, F;Casano, L;Malhotra, V
通讯作者：
Malhotra, V