Angara Rajendra Kumar, Sadi Arif, Gilk Stacey D
Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA.
EMBO Rep. 2024 Dec;25(12):5331-5351. doi: 10.1038/s44319-024-00266-8. Epub 2024 Sep 27.
Effective intracellular communication between cellular organelles occurs at dedicated membrane contact sites (MCSs). Tether proteins are responsible for the establishment of MCSs, enabling direct communication between organelles to ensure organelle function and host cell homeostasis. While recent research has identified tether proteins in several bacterial pathogens, their functions have predominantly been associated with mediating inter-organelle communication between the bacteria containing vacuole (BCV) and the host endoplasmic reticulum (ER). Here, we identify a novel bacterial effector protein, CbEPF1, which acts as a molecular tether beyond the confines of the BCV and facilitates interactions between host cell organelles. Coxiella burnetii, an obligate intracellular bacterial pathogen, encodes the FFAT motif-containing protein CbEPF1 which localizes to host lipid droplets (LDs). CbEPF1 establishes inter-organelle contact sites between host LDs and the ER through its interactions with VAP family proteins. Intriguingly, CbEPF1 modulates growth of host LDs in a FFAT motif-dependent manner. These findings highlight the potential for bacterial effector proteins to impact host cellular homeostasis by manipulating inter-organelle communication beyond conventional BCVs.
细胞内细胞器之间有效的细胞内通讯发生在特定的膜接触位点（MCSs）。系链蛋白负责建立MCSs，使细胞器之间能够直接通讯，以确保细胞器功能和宿主细胞的稳态。虽然最近的研究已经在几种细菌病原体中鉴定出系链蛋白，但其功能主要与介导含细菌液泡（BCV）与宿主内质网（ER）之间的细胞器间通讯有关。在这里，我们鉴定出一种新型细菌效应蛋白CbEPF1，它作为一种分子系链，超出了BCV的范围，并促进宿主细胞器之间的相互作用。专性细胞内细菌病原体伯氏考克斯氏体编码含FFAT基序的蛋白CbEPF1，该蛋白定位于宿主脂滴（LDs）。CbEPF1通过与VAP家族蛋白相互作用，在宿主LDs和ER之间建立细胞器间接触位点。有趣的是，CbEPF1以FFAT基序依赖的方式调节宿主LDs的生长。这些发现突出了细菌效应蛋白通过操纵超越传统BCV的细胞器间通讯来影响宿主细胞稳态的潜力。
