Eukaryotic Clathrin Adapter Protein and Mediator of Cholesterol Homeostasis, PICALM, Affects Trafficking to the Chlamydial Inclusion.
Eukaryotic Clathrin Adapter Protein and Mediator of Cholesterol Homeostasis, PICALM, Affects Trafficking to the Chlamydial Inclusion.
复制标题
真核网格蛋白接头蛋白和胆固醇稳态介质 PICALM 影响衣原体包涵体的运输。
DOI：
10.1080/10985549.2023.2171695
复制
发表时间：
2023
影响因子：
5.3
通讯作者：
Rucks,ElizabethA
中科院分区：
文献类型：
--
作者：
Jorgenson,LisaM;Knight,Lindsey;Widner,RayE;Rucks,ElizabethA
专性细胞内病原体沙眼衣原体从宿主细胞内包涵体开始经历其双相发育周期时具有独特的代谢要求。在我们以前的研究中，我们确定了宿主蛋白，PICALM，它定位于衣原体包涵体。PICALM在许多宿主途径中起作用，包括受体、特异性SNARE蛋白和转铁蛋白等分子的再循环，以及维持胆固醇稳态。因此，我们假设PICALM的功能是维持胆固醇含量，并调节从内体再循环途径到包涵体的转运，这控制衣原体进入该途径。在未感染的细胞中，PICALM的siRNA敲低导致高尔基体和转铁蛋白受体（TfR）阳性囊泡（再循环内体）内胆固醇增加。在感染C.沙眼导致高尔基体衍生的脂质和蛋白质、转铁蛋白、转铁蛋白和Rab 11-FIP 1定位于包涵体的水平增加，高尔基体碎片化和Rab 11运输到包涵体的减少。有趣的是，单独的衣原体感染也会增加TfR和Rab 11相关囊泡中的胆固醇，而PICALM敲减则会逆转这种效应。我们的数据表明，PICALM的功能，以平衡或限制衣原体进入多个亚细胞运输途径，以维持健康的宿主细胞在衣原体感染。
The obligate intracellular pathogenChlamydia trachomatishas unique metabolic requirements as it proceeds through its biphasic developmental cycle from within the inclusion within the host cell. In our previous study, we identified a host protein, PICALM, which localizes to the chlamydial inclusion. PICALM functions in many host pathways including the recycling of receptors, specific SNARE proteins, and molecules like transferrin, and maintaining cholesterol homeostasis. Hence, we hypothesized that PICALM functions to maintain the cholesterol content and to moderate trafficking from the endosomal recycling pathway to the inclusion, which controls chlamydial access to this pathway. In uninfected cells, siRNA knockdown of PICALM resulted in increased cholesterol within the Golgi and transferrin receptor (TfR) positive vesicles (recycling endosomes). PICALM knockdown in cells infected withC. trachomatisresulted in increased levels of Golgi-derived lipid and protein, TfR, transferrin, and Rab11-FIP1 localized to inclusions and a decrease of Golgi fragmentation at and Rab11 trafficking to the inclusion. Interestingly, chlamydial infection alone also increases cholesterol in TfR and Rab11-associated vesicles, and PICALM knockdown reverses this effect. Our data suggest that PICALM functions to balance or limit chlamydial access to multiple subcellular trafficking pathways to maintain the health of the host cell during chlamydial infection.