Legionella pneumophila LegC7 effector protein drives aberrant endoplasmic reticulum:endosome contacts in yeast.
Legionella pneumophila LegC7 effector protein drives aberrant endoplasmic reticulum:endosome contacts in yeast.
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DOI：
10.1111/tra.12807
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Starai VJ
中科院分区：
文献类型：
--
作者：
Glueck NK;O'Brien KM;Seguin DC;Starai VJ
嗜肺军团菌是一种兼性的细胞内细菌病原体，可引起被称为军团病的严重肺炎。军团菌通过IVB型分泌系统分泌的“效应器”蛋白主动改变宿主细胞器的运输，从而构建富含细菌的军团菌空泡(LCV)，防止溶酶体的降解。LCV是由来自宿主内质网、分泌囊泡和吞噬小体的膜创建的，尽管驱动其合成的确切分子机制仍不清楚。为了在酵母真核膜运输的背景下表征军团菌LegC7/Ylfa陷阱样效应蛋白的体内活性，我们发现LegC7与Emp46p/Emp47p ER-to-Golgi糖蛋白货物适配器复合体相互作用，改变ER的形态，并诱导异常的ER：内体相互作用，通过ER货物降解、分裂GFP蛋白的重组和ER管腔的增强氧化来测量。LegC7依赖的毒性、内质网形态的破坏和内质网：内体融合事件依赖于内体VPS C类锚定复合体和内体T-SNARE，Pep12p。本工作建立了一个模型，在该模型中，LegC7通过驱动ER：内小体接触，可能通过与宿主膜系留复合体和/或货物适配器的相互作用，在感染过程中将宿主ER物质招募到细菌吞噬小体中。
Legionella pneumophila is a facultative intracellular bacterial pathogen, causing the severe form of pneumonia known as Legionnaires’ disease. Legionella actively alters host organelle trafficking through the activities of ‘effector’ proteins secreted via a TypeIVB secretion system, in order to construct the bacteria-laden Legionella-containing vacuole (LCV) and prevent lysosomal degradation. The LCV is created with membrane derived from host ER, secretory vesicles, and phagosomes, although the precise molecular mechanisms that drive its synthesis remain poorly understood. In an effort to characterize the in vivo activity of the LegC7/YlfA SNARE-like effector protein from Legionella in the context of eukaryotic membrane trafficking in yeast, we find that LegC7 interacts with the Emp46p/Emp47p ER-to-Golgi glycoprotein cargo adapter complex, alters ER morphology, and induces aberrant ER:endosome interactions, as measured by visualization of ER cargo degradation, reconstitution of split-GFP proteins, and enhanced oxidation of the ER lumen. LegC7-dependent toxicity, disruption of ER morphology, and ER:endosome fusion events were dependent upon endosomal VPS class C tethering complexes and the endosomal t-SNARE, Pep12p. This work establishes a model in which LegC7 functions to recruit host ER material to the bacterial phagosome during infection by driving ER:endosome contacts, potentially through interaction with host membrane tethering complexes and/or cargo adapters.
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DOI：
10.1126/science.1227026
发表时间：
2012-11-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Choy A;Dancourt J;Mugo B;O'Connor TJ;Isberg RR;Melia TJ;Roy CR
通讯作者：
Roy CR
酵母EMP47P的高尔基体定位取决于其二赖氨酸基序，但不受α-COP中RET1-1突变的影响。
影响因子：
7.8
作者：
SCHRODER, S;SCHIMMOLLER, F;SINGERKRUGER, B;RIEZMAN, H
通讯作者：
RIEZMAN, H
影响因子：
64.8
作者：
Babu, Mohan;Vlasblom, James;Greenblatt, Jack F.
通讯作者：
Greenblatt, Jack F.
影响因子：
64.5
作者：
JOHNSON, LM;BANKAITIS, VA;EMR, SD
通讯作者：
EMR, SD
DOI：
10.1073/pnas.0509035102
发表时间：
2005-12-13
影响因子：
11.1
作者：
Austin, CD;Wen, XH;Scales, SJ
通讯作者：
Scales, SJ