Sorting nexin-1 defines an early phase of Salmonella-containing vacuole-remodeling during Salmonella infection
Sorting nexin-1 defines an early phase of Salmonella-containing vacuole-remodeling during Salmonella infection
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DOI：
10.1242/jcs.018432
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发表时间：
2008-06-15
影响因子：
4
通讯作者：
Cullen, Peter J.
中科院分区：
文献类型：
--
作者：
Bujny, Miriam V.;Ewels, Phil A.;Cullen, Peter J.
肠炎沙门氏菌血清型鼠伤寒沙门氏菌在宿主细胞内的一个特殊的膜结合室中复制，即含沙门氏菌液泡（SCV）。scv与宿主内吞网络的相互作用由细菌效应物调节，其中一些效应物，如SigD/SopB，操纵内体磷酸肌苷的水平。在这里，我们确定在沙门氏菌感染的早期阶段，分选连接蛋白-1 (SNX1) -一种宿主磷肌苷结合蛋白，通常与早期内体结合并调节转运到反式高尔基网络(TGN)-经历快速和短暂的易位到细菌进入位点，这一事件由SigD/SopB促进。SNX1向scv的募集导致形成广泛的、长距离的小管，我们称之为“宽敞的液泡相关小管”。这些小管的形成伴随着液泡大小的减小和tgn驻留货物的去除。SNX1抑制干扰细菌的胞内进程，导致复制延迟。我们认为SNX1在新生scv的管状重建中很重要，并在此过程中调节细胞内细菌的进展和复制。
Salmonella enterica serovar Typhimurium replicate within host cells in a specialized membrane-bound compartment, the Salmonella-containing vacuole (SCV). Interaction of SCVs with the host endocytic network is modulated by bacterial effectors, some of which, such as SigD/SopB, manipulate the level of endosomal phosphoinositides. Here, we establish that at early stages of Salmonella infection, sorting nexin-1 (SNX1) - a host phosphoinositide-binding protein that normally associates with early endosomes and regulates transport to the trans-Golgi network (TGN)-undergoes a rapid and transient translocation to bacterial entry sites, an event promoted by SigD/SopB. Recruitment of SNX1 to SCVs results in the formation of extensive, long-range tubules that we have termed 'spacious vacuole-associated tubules'. Formation of these tubules is coupled with size reduction of vacuoles and the removal of TGN-resident cargo. SNX1 suppression perturbs intracellular progress of bacteria, resulting in a delayed replication. We propose that SNX1 is important in tubular-based re-modeling of nascent SCVs and, in doing so, regulates intracellular bacterial progression and replication.