Intracellular pathogens survive in eukaryotic cells by evading a variety of host defences. To avoid degradation through the endocytic pathway, intracellular bacteria must adapt their phagosomes into protective compartments that promote bacterial replication. Legionella pneumophila and Coxiella burnetii are Gram-negative intracellular pathogens that remodel their phagosomes by co-opting components of the host cell, including Rab GTPases. L. pneumophila and C. burnetii are related phylogenetically and share an analogous type IV secretion system for delivering bacterial effectors into the host cell. Some of these effectors mimic eukaryotic biochemical activities to recruit and modify Rabs at the vacuole. In the present review, we cover how these bacterial species, which utilize divergent strategies to establish replicative vacuoles, use translocated proteins to manipulate host Rabs, as well as exploring which Rabs are implicated in vacuolar biogenesis in these two organisms.
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http://dx.doi.org/10.1042/BST20120167 | DOI Listing |
Proc Natl Acad Sci U S A
February 2025
Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.
Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1) are associated with familial Parkinson's disease (PD). LRRK2 phosphorylates Rab guanosine triphosphatase (GTPases) within the Switch II domain while PINK1 directly phosphorylates Parkin and ubiquitin (Ub) and indirectly induces phosphorylation of a subset of Rab GTPases. Herein we have crossed LRRK2 [R1441C] mutant knock-in mice with PINK1 knock-out (KO) mice and report that loss of PINK1 does not impact endogenous LRRK2-mediated Rab phosphorylation nor do we see significant effect of mutant LRRK2 on PINK1-mediated Rab and Ub phosphorylation.
View Article and Find Full Text PDFJ Cell Biol
April 2025
Department of Genetics and Cell Biology, College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China.
TBC1D20 deficiency causes Warburg Micro Syndrome in humans, characterized by multiple eye abnormalities, severe intellectual disability, and abnormal sexual development, but the molecular mechanisms remain unknown. Here, we identify TBC1D20 as a novel Rab11 GTPase-activating protein that coordinates vesicle transport and actin remodeling to regulate ciliogenesis. Depletion of TBC1D20 promotes Rab11 vesicle accumulation and actin deconstruction around the centrosome, facilitating the initiation of ciliogenesis even in cycling cells.
View Article and Find Full Text PDFJ Extracell Vesicles
January 2025
Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts, USA.
Extracellular vesicles (EVs) from brain-seeking breast cancer cells (Br-EVs) breach the blood-brain barrier (BBB) via transcytosis and promote brain metastasis. Here, we defined the mechanisms by which Br-EVs modulate brain endothelial cell (BEC) dynamics to facilitate their BBB transcytosis. BEC treated with Br-EVs show significant downregulation of Rab11fip2, known to promote vesicle recycling to the plasma membrane and significant upregulation of Rab11fip3 and Rab11fip5, which support structural stability of the endosomal compartment and facilitate vesicle recycling and transcytosis, respectively.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Experimental Medicine, University of Salento, Via Provinciale Lecce-Monteroni n. 165, 73100 Lecce, Italy.
Peripherin belongs to heterogeneous class III of intermediate filaments, and it is the only intermediate filament protein selectively expressed in the neurons of the peripheral nervous system. It has been previously discovered that peripherin interacts with proteins important for the endo-lysosomal system and for the transport to late endosomes and lysosomes, such as RAB7A and AP-3, although little is known about its role in the endocytic pathway. Here, we show that peripherin silencing affects lysosomal abundance but also positioning, causing the redistribution of lysosomes from the perinuclear area to the cell periphery.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
January 2025
Department of Neurosurgery, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background: Ovarian cancer (OC) progression is one of the commonest cause of female cancer death. While treatments in clinic includes primary surgery and targeted chemotherapy, curative and survival trends in OC have not significantly improved. Thus, further investigation of the mechanisms regarding OC carcinogenesis and discovery of novel targets is of great importance.
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