Rapamycin Re-Directs Lysosome Network, Stimulates ER-Remodeling, Involving Membrane CD317 and Affecting Exocytosis, in Campylobacter Jejuni-Lysate-Infected U937 Cells
Open Access
- 23 March 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (6), 2207
- https://doi.org/10.3390/ijms21062207
Abstract
The Gram-negative Campylobacter jejuni is a major cause of foodborne gastroenteritis in humans worldwide. The cytotoxic effects of Campylobacter have been mainly ascribed to the actions of the cytolethal distending toxin (CDT): it is mandatory to put in evidence risk factors for sequela development, such as reactive arthritis (ReA) and Guillain–Barré syndrome (GBS). Several researches are directed to managing symptom severity and the possible onset of sequelae. We found for the first time that rapamycin (RM) is able to largely inhibit the action of C. jejuni lysate CDT in U937 cells, and to partially avoid the activation of specific sub-lethal effects. In fact, we observed that the ability of this drug to redirect lysosomal compartment, stimulate ER-remodeling (highlighted by ER–lysosome and ER–mitochondria contacts), protect mitochondria network, and downregulate CD317/tetherin, is an important component of membrane microdomains. In particular, lysosomes are involved in the process of the reduction of intoxication, until the final step of lysosome exocytosis. Our results indicate that rapamycin confers protection against C. jejuni bacterial lysate insults to myeloid cells.This publication has 106 references indexed in Scilit:
- Retinoblastoma protein regulates the crosstalk between autophagy and apoptosis, and favors glioblastoma resistance to etoposideCell Death & Disease, 2013
- Campylobacter jejuni Induces Colitis Through Activation of Mammalian Target of Rapamycin SignalingGastroenterology, 2012
- Mechanisms controlling granule-mediated cytolytic activity of cytotoxic T lymphocytesImmunologic Research, 2011
- mTORC1 serves ER stress-triggered apoptosis via selective activation of the IRE1–JNK pathwayCell Death & Differentiation, 2011
- Lysosomal positioning coordinates cellular nutrient responsesNature, 2011
- Cytolethal Distending Toxin Family Members Are Differentially Affected by Alterations in Host Glycans and Membrane CholesterolOnline Journal of Public Health Informatics, 2010
- Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7–RILP–p150Glued and late endosome positioningThe Journal of cell biology, 2009
- HM1.24 Is Internalized from Lipid Rafts by Clathrin-mediated Endocytosis through Interaction with α-AdaptinOnline Journal of Public Health Informatics, 2009
- Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translationProceedings of the National Academy of Sciences of the United States of America, 2008
- Stress and IGF-I Differentially Control Cell Fate through Mammalian Target of Rapamycin (mTOR) and Retinoblastoma Protein (pRB)Online Journal of Public Health Informatics, 2008