The lipid transfer protein CERT interacts with the Chlamydia inclusion protein IncD and participates to ER-Chlamydia inclusion membrane contact sites.
The lipid transfer protein CERT interacts with the Chlamydia inclusion protein IncD and participates to ER-Chlamydia inclusion membrane contact sites.
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DOI：
10.1371/journal.ppat.1002092
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发表时间：
2011-06
期刊：
影响因子：
6.7
通讯作者：
Agaisse H
中科院分区：
文献类型：
--
作者：
Derré I;Swiss R;Agaisse H
驻留在膜结合室的细菌病原体操纵宿主细胞机制来建立和维持它们的细胞内生态位。通过靶向小的GTP酶或SNARE蛋白来劫持细胞器间的囊泡运输已经得到了很好的证实。在这里，我们表明，细胞内的病原体也建立与细胞器的直接膜接触部位，并利用非囊泡运输机制。我们确定内质网到高尔基神经酰胺转移蛋白CERT是一种宿主细胞因子，特异性地招募到包涵体，一个膜结合的隔室，含有专性的细胞内病原体沙眼衣原体。我们进一步表明，CERT对包涵体的募集与包涵膜附近VAPA/B阳性小管的募集相关，表明沙眼衣原体感染时形成了ER-包涵膜接触部位。此外，我们还发现沙眼衣原体效应蛋白IncD是CERT的特异性结合伙伴。最后，我们发现CERT或VAP蛋白的缺失会损害细菌的发育。我们认为，IncD、CERT、VAPA/B和潜在的额外宿主和/或细菌因子的存在，在内质网和包涵体膜之间的接触点提供了有利于细菌发育的专门的代谢和/或信号微环境。专性细胞内细菌病原体衣原体已经发展出入侵、生存和在宿主生殖器、眼和肺上皮表面复制的策略。衣原体的发育周期发生在一个膜结合的液泡中，包涵体。包涵体膜依赖衣原体的重塑导致一个独特和专门的隔室，允许与细胞器进行特定的相互作用，并获得细菌生存和复制所需的分子和营养物质。这项研究提供了一个例子，说明将沙眼衣原体蛋白插入包涵膜可能会允许细菌操纵宿主细胞，使其受益。我们发现脂转移蛋白CERT定位于沙眼衣原体包涵膜，并与内质网蛋白VAPB部分共定位。此外，VAPB阳性小管与包涵膜紧密接触，提示沙眼衣原体感染时可形成ER-包涵膜接触点。最后，我们发现CERT与沙眼衣原体包涵体蛋白IncD相互作用。我们认为，CERT、VAPB和IncD在内质网包涵体膜接触点的存在使沙眼衣原体能够利用宿主细胞的非囊泡性脂质运输机制，产生有利于细菌发育的代谢和信号事件的专门平台。
Bacterial pathogens that reside in membrane bound compartment manipulate the host cell machinery to establish and maintain their intracellular niche. The hijacking of inter-organelle vesicular trafficking through the targeting of small GTPases or SNARE proteins has been well established. Here, we show that intracellular pathogens also establish direct membrane contact sites with organelles and exploit non-vesicular transport machinery. We identified the ER-to-Golgi ceramide transfer protein CERT as a host cell factor specifically recruited to the inclusion, a membrane-bound compartment harboring the obligate intracellular pathogen Chlamydia trachomatis. We further showed that CERT recruitment to the inclusion correlated with the recruitment of VAPA/B-positive tubules in close proximity of the inclusion membrane, suggesting that ER-Inclusion membrane contact sites are formed upon C. trachomatis infection. Moreover, we identified the C. trachomatis effector protein IncD as a specific binding partner for CERT. Finally we showed that depletion of either CERT or the VAP proteins impaired bacterial development. We propose that the presence of IncD, CERT, VAPA/B, and potentially additional host and/or bacterial factors, at points of contact between the ER and the inclusion membrane provides a specialized metabolic and/or signaling microenvironment favorable to bacterial development. The obligate intracellular bacterial pathogen Chlamydia has developed strategies to invade, survive and replicate within the host genital, ocular and pulmonary epithelial surfaces. Chlamydia developmental cycle occurs in a membrane bound vacuole, the inclusion. The Chlamydia-dependent remodeling of the inclusion membrane leads to a unique and specialized compartment that allows for the specific interaction with cellular organelles and the acquisition of molecules and nutrients required for bacterial survival and replication. This study provides an example of how the insertion of C. trachomatis proteins into the inclusion membrane may allow the bacteria to manipulate the host cells to its own benefit. We showed that the lipid transfer protein CERT localized to C. trachomatis inclusion membrane and partly co-localized with the endoplasmic reticulum (ER) protein VAPB. Moreover, VAPB positive tubules made close contact with the inclusion membrane, suggesting the formation of ER-Inclusion membrane contact sites upon C. trachomatis infection. Finally, we have shown that CERT interacted with the C. trachomatis inclusion protein IncD. We propose that the presence of CERT, VAPB and IncD at ER-Inclusion membrane contact sites allow C. trachomatis to exploit the non-vesicular lipid transport machinery of the host cell and generate platforms specialized in metabolism and signaling events favorable to bacterial development.
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DOI：
10.1111/j.1600-0854.2008.00810.x
发表时间：
2008-11
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Chandran S;Machamer CE
通讯作者：
Machamer CE
影响因子：
2.9
作者：
Garcia, P;Gupta, R;Rebecchi, MJ
通讯作者：
Rebecchi, MJ
DOI：
10.1073/pnas.92.11.4877
发表时间：
1995-05-23
影响因子：
11.1
作者：
HACKSTADT, T;SCIDMORE, MA;ROCKEY, DD
通讯作者：
ROCKEY, DD
影响因子：
21.3
作者：
Kanai, F;Liu, H;Yaffe, MB
通讯作者：
Yaffe, MB
影响因子：
6.7
作者：
Elwell, Cherilyn A.;Ceesay, Alhaji;Kim, Jung Hwa;Kalman, Daniel;Engel, Joanne N.
通讯作者：
Engel, Joanne N.