The Anaplasma phagocytophilum-occupied vacuole selectively recruits Rab-GTPases that are predominantly associated with recycling endosomes.
The Anaplasma phagocytophilum-occupied vacuole selectively recruits Rab-GTPases that are predominantly associated with recycling endosomes.
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DOI：
10.1111/j.1462-5822.2010.01468.x
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发表时间：
2010-09-01
影响因子：
3.4
通讯作者：
Carlyon JA
中科院分区：
文献类型：
--
作者：
Huang B;Hubber A;McDonough JA;Roy CR;Scidmore MA;Carlyon JA
嗜吞噬细胞无形体是一种专性细胞内细菌，感染中性粒细胞，使其驻留在宿主细胞衍生的空泡内。助理嗜吞噬细胞占据的空泡（ApV）不能沿着内吞途径成熟，并且不与溶酶体融合。Rab GTP酶调节膜运输。为了更好地理解细菌如何调节ApV的选择性融合性，我们检测了20个绿色荧光蛋白（GFP）或红色荧光蛋白（RFP）标记的Rab GTP酶在A.嗜吞噬细胞菌感染HL-60细胞。GFP-Rab 4A、GFP-Rab 10、GFP-Rab 11 A、GFP-Rab 14、RFP-Rab 22 A和GFP-Rab 35调节内吞再循环，GFP-Rab 1介导内质网到高尔基体的运输，定位于ApV。在ApV形成后，经标记的Rabs被募集到ApV中，并在整个感染过程中保持相关。内源性Rab 14定位于ApV。四环素治疗伴随促进再循环内体相关GFP-Rab的损失和GFP-Rab 5、GFP-Rab 7和溶酶体标志物LAMP-1的获得。野生型和GTP酶缺陷型的GFP-Rab 1、GFP-Rab 4A和GFP-Rab 11 A定位于ApV，但不定位于GDP限制型的GFP-Rab 1、GFP-Rab 4A和GFP-Rab 11 A。引人注目的是，GFP-Rab 10募集到ApV是不依赖于鸟嘌呤核苷酸的。这些数据表明A.嗜吞噬细胞菌选择性地募集Rab GTP酶，其主要与再循环内体相关以促进其细胞内存活，并涉及细菌蛋白质调节ApV上的Rab 10膜循环。
Anaplasma phagocytophilum is an obligate intracellular bacterium that infects neutrophils to reside within a host cell-derived vacuole. The A. phagocytophilum-occupied vacuole (ApV) fails to mature along the endocytic pathway and is non-fusogenic with lysosomes. Rab GTPases regulate membrane traffic. To better understand how the bacterium modulates the ApV’s selective fusogencity, we examined the intracellular localization of 20 green fluorescent protein (GFP) or red fluorescent protein (RFP)-tagged Rab GTPases in A. phagocytophilum infected HL-60 cells. GFP-Rab4A, GFP-Rab10, GFP-Rab11A, GFP-Rab14, RFP-Rab22A, and GFP-Rab35, which regulate endocytic recycling, and GFP-Rab1, which mediates endoplasmic reticulum to Golgi apparatus trafficking, localize to the ApV. Fluorescently tagged Rabs are recruited to the ApV upon its formation and remain associated throughout infection. Endogenous Rab14 localizes to the ApV. Tetracycline treatment concomitantly promotes loss of recycling endosome-associated GFP-Rabs and acquisition of GFP-Rab5, GFP-Rab7, and the lysosomal marker, LAMP-1. Wild-type and GTPase-deficient versions, but not GDP-restricted versions of GFP-Rab1, GFP-Rab4A, and GFP-Rab11A localize to the ApV. Strikingly, GFP-Rab10 recruitment to the ApV is guanine nucleotide-independent. These data establish that A. phagocytophilum selectively recruits Rab GTPases that are primarily associated with recycling endosomes to facilitate its intracellular survival and implicate bacterial proteins in regulating Rab10 membrane cycling on the ApV.
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影响因子：
4.5
作者：
Dunning Hotopp JC;Lin M;Madupu R;Crabtree J;Angiuoli SV;Eisen JA;Seshadri R;Ren Q;Wu M;Utterback TR;Smith S;Lewis M;Khouri H;Zhang C;Niu H;Lin Q;Ohashi N;Zhi N;Nelson W;Brinkac LM;Dodson RJ;Rosovitz MJ;Sundaram J;Daugherty SC;Davidsen T;Durkin AS;Gwinn M;Haft DH;Selengut JD;Sullivan SA;Zafar N;Zhou L;Benahmed F;Forberger H;Halpin R;Mulligan S;Robinson J;White O;Rikihisa Y;Tettelin H
通讯作者：
Tettelin H
影响因子：
3.1
作者：
Cortes, Claudio;Rzomp, Mmberly A.;Wizel, Benjamin
通讯作者：
Wizel, Benjamin
细菌效应器设计和功能的常见主题。
影响因子：
30.3
作者：
Galan, Jorge E.
通讯作者：
Galan, Jorge E.
内吞囊泡中的甘露糖6-磷酸受体和溶酶体膜蛋白的分选。
影响因子：
7.8
作者：
Geuze, H J;Stoorvogel, W;Strous, G J;Slot, J W;Bleekemolen, J E;Mellman, I
通讯作者：
Mellman, I
影响因子：
11.4
作者：
Kyei, George B.;Vergne, Isabelle;Deretic, Vojo
通讯作者：
Deretic, Vojo