scholarly journals Disruption of vacuolin microdomains in the host Dictyostelium discoideum increases resistance to Mycobacterium marinum-induced membrane damage and infection

2021 ◽  
Author(s):  
Cristina Bosmani ◽  
Angélique Perret ◽  
Florence Leuba ◽  
Aurélie Guého ◽  
Nabil Hanna ◽  
...  
Keyword(s):  
Dictyostelium Discoideum ◽  
Membrane Damage ◽  
Mycobacterium Marinum ◽  
Vesicular Trafficking ◽  
Membrane Microdomains ◽  
Membrane Association ◽  
Phagosome Maturation ◽  
Closely Related Species ◽  
Important Host ◽  
And Function

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, manipulates the host phagosome maturation pathway to replicate intracellularly. Mycobacterium marinum, a closely-related species, and Dictyostelium discoideum, a social amoeba and alternative phagocytic host, have been used as models to study host-pathogen interactions occurring during mycobacterial infections. Vacuolins, functional homologues of the mammalian flotillins, organize membrane microdomains and play a role in vesicular trafficking. Various pathogens have been reported to manipulate their membrane association and function. During infection of D. discoideum with M. marinum, Vacuolin C was specifically and highly induced and all three vacuolin isoforms were enriched at the mycobacteria-containing-vacuole (MCV). In addition, absence of vacuolins reduced escape from the MCV and conferred resistance to M. marinum infection. Moreover, ESAT-6, the membrane-disrupting virulence factor of M. marinum, was less associated with membranes when vacuolins were absent. Together, these results suggest that vacuolins are important host factors that are manipulated by mycobacteria to inflict membrane damage and escape from their compartment.

scholarly journals The Dictyostelium discoideum E3 ubiquitin ligase TrafE coordinates endolysosomal damage response and cell-autonomous immunity to Mycobacterium marinum.

2021 ◽  
Author(s):  
Lyudmil Raykov ◽  
Manon Mottet ◽  
Jahn Nitschke ◽  
Thierry Soldati
Keyword(s):  
Cell Death ◽  
Dictyostelium Discoideum ◽  
Cellular Response ◽  
Membrane Damage ◽  
Mycobacterium Marinum ◽  
Chemical Components ◽  
Key Factors ◽  
Endosomal Sorting ◽  
Damage Response ◽  
Intracellular Compartments

Cells are perpetually challenged by pathogens, protein aggregates or chemicals, that induce plasma membrane or endolysosomal compartments damage. Endolysosomal perforations are recognised as severe stress, however the mechanisms of the cellular response that ensure quality control, repair and endolysosomal homeostasis are just beginning to be unravelled. The endosomal sorting complex required for transport (ESCRT) and the autophagy machinery are recruited to damaged membranes to either repair or to remove membrane remnants. Crucial element of the endolysosomal damage response (ELDR) are factors that sense damage, paralleled by extensive tagging of the damaged organelles with signals, such as ubiquitin, required for the recruitment of ELDR components. Unattended membrane damage leads to leakage of harmful components including protons and reactive oxygen species that cause cell death. To explore ELDR key factors responsible for detection and marking of damaged compartments we use the professional phagocyte Dictyostelium discoideum. We found an evolutionary conserved E3-ligase TrafE that is robustly recruited to intracellular compartments disrupted after infection with Mycobacterium marinum or after sterile damage caused by chemical components. Importantly, we show that the absence of TrafE severely compromises the xenophagy restriction of bacteria as well as autophagy-mediated and ESCRT-mediated ELDR, resulting in early cell death.

scholarly journals Proteomic characterization of the Mycobacterium marinum-containing vacuole in Dictyostelium discoideum

2019 ◽  
Author(s):  
Aurélie Guého ◽  
Cristina Bosmani ◽  
Thierry Soldati
Keyword(s):  
Dictyostelium Discoideum ◽  
Model System ◽  
Mycobacterium Marinum ◽  
Close Relative ◽  
Phagosome Maturation ◽  
Fish Pathogen ◽  
Free Living ◽  
Free Living Amoeba ◽  
Professional Phagocyte

ABSTRACTMycobacterium tuberculosis, the causative agent of tuberculosis, is able to manipulate the phagosome compartment where it resides in order to establish a permissive replicative compartment called the Mycobacterium-containing vacuole (MCV). Mycobacterium marinum, a fish pathogen and a close relative of the tuberculosis group, is also able to infect the free-living amoeba and professional phagocyte Dictyostelium discoideum and to manipulate its phagosome maturation. By using this host/pathogen model system, we have established an innovative procedure to isolate MCVs. This procedure allowed us to isolate M. marinum-MCV at 1, 3 and 6 hours post infection to study the early M. marinum-MCV proteome. By using isobaric labelling and mass spectrometry, we quantitatively compared the proteomic composition of those MCVs isolated at different stages of the early infection phase to understand how M. marinum impacts on this compartment to divert it from the normal phagosomal pathway. Furthermore, we also compare the manipulated compartment M. marinum-MCV to non- or less manipulated compartments containing different mycobacteria strains: the non-pathogenic M. smegmatis, the avirulent M. marinum-L1D or the attenuated M. marinum-RD1.

scholarly journals ESCRT and autophagy cooperate to repair ESX-1-dependent damage to the Mycobacterium-containing vacuole

2018 ◽  
Author(s):  
Ana T. López-Jiménez ◽  
Elena Cardenal-Muñoz ◽  
Florence Leuba ◽  
Lilli Gerstenmaier ◽  
Monica Hagedorn ◽  
...  
Keyword(s):  
Dictyostelium Discoideum ◽  
Membrane Damage ◽  
Mycobacterium Marinum ◽  
Eukaryotic Cells ◽  
Intracellular Pathogens ◽  
Membrane Repair ◽  
Endosomal Sorting

AbstractPhagocytes capture invader microbes within the bactericidal phagosome. Some pathogens subvert killing by damaging and escaping from this compartment. To prevent and fight bacterial escape, cells contain and repair the membrane damage, or finally eliminate the cytosolic escapees. All eukaryotic cells engage highly conserved mechanisms to ensure integrity of membranes in a multitude of physiological and pathological situations, including the Endosomal Sorting Complex Required for Transport (ESCRT) and autophagy machineries. In Dictyostelium discoideum, recruitment of the ESCRT-III protein Snf7/Chmp4/Vps32 and the ATPase Vps4 to sites of membrane repair relies on the ESCRT-I component Tsg101 and occurs in absence of Ca2+. The ESX-1 dependent membrane perforations produced by the pathogen Mycobacterium marinum separately engage both ESCRT and autophagy. In absence of Tsg101, M. marinum escapes earlier to the cytosol, where it is restricted by xenophagy. We propose that ESCRT has an evolutionary conserved function in containing intracellular pathogens in intact compartments.

scholarly journals How Can Satellite DNA Divergence Cause Reproductive Isolation? Let Us Count the Chromosomal Ways

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Patrick M. Ferree ◽  
Satyaki Prasad
Keyword(s):  
Reproductive Isolation ◽  
Developmental Stages ◽  
Rapid Evolution ◽  
Model Organisms ◽  
Cellular Mechanisms ◽  
Closely Related Species ◽  
Heterochromatin Formation ◽  
Interspecies Hybrids ◽  
Postzygotic Reproductive Isolation ◽  
And Function

Satellites are one of the most enigmatic parts of the eukaryotic genome. These highly repetitive, noncoding sequences make up as much as half or more of the genomic content and are known to play essential roles in chromosome segregation during meiosis and mitosis, yet they evolve rapidly between closely related species. Research over the last several decades has revealed that satellite divergence can serve as a formidable reproductive barrier between sibling species. Here we highlight several key studies on Drosophila and other model organisms demonstrating deleterious effects of satellites and their rapid evolution on the structure and function of chromosomes in interspecies hybrids. These studies demonstrate that satellites can impact chromosomes at a number of different developmental stages and through distinct cellular mechanisms, including heterochromatin formation. These findings have important implications for how loci that cause postzygotic reproductive isolation are viewed.

scholarly journals Retromer has a selective function in cargo sorting via endosome transport carriers

2018 ◽  
Vol 218 (2) ◽  
pp. 615-631 ◽  
Author(s):  
Yi Cui ◽  
Julian M. Carosi ◽  
Zhe Yang ◽  
Nicholas Ariotti ◽  
Markus C. Kerr ◽  
...  
Keyword(s):  
Vesicular Trafficking ◽  
Lysosomal Hydrolases ◽  
Cell Level ◽  
Ultrastructural Alteration ◽  
Membrane Protein Complex ◽  
Lysosomal Function ◽  
Trafficking Pathway ◽  
Peripheral Membrane Protein ◽  
And Function ◽  
Proteolytic Capacity

Retromer is a peripheral membrane protein complex that coordinates multiple vesicular trafficking events within the endolysosomal system. Here, we demonstrate that retromer is required for the maintenance of normal lysosomal morphology and function. The knockout of retromer subunit Vps35 causes an ultrastructural alteration in lysosomal structure and aberrant lysosome function, leading to impaired autophagy. At the whole-cell level, knockout of retromer Vps35 subunit reduces lysosomal proteolytic capacity as a consequence of the improper processing of lysosomal hydrolases, which is dependent on the trafficking of the cation-independent mannose 6-phosphate receptor (CI-M6PR). Incorporation of CI-M6PR into endosome transport carriers via a retromer-dependent process is restricted to those tethered by GCC88 but not golgin-97 or golgin-245. Finally, we show that this retromer-dependent retrograde cargo trafficking pathway requires SNX3, but not other retromer-associated cargo binding proteins, such as SNX27 or SNX-BAR proteins. Therefore, retromer does contribute to the retrograde trafficking of CI-M6PR required for maturation of lysosomal hydrolases and lysosomal function.

scholarly journals Inter-species comparison of the orientation algorithm directing larval chemotaxis in the genus Drosophila

2021 ◽  
Author(s):  
Elie Fink ◽  
Matthieu Louis
Keyword(s):  
Neural Circuits ◽  
Rapid Evolution ◽  
Structure And Function ◽  
Olfactory Behavior ◽  
Species Comparison ◽  
Closely Related Species ◽  
Genetic Studies ◽  
Phenotypic Differences ◽  
Peripheral Olfactory System ◽  
And Function

Animals differ in their appearances and behaviors. While many genetic studies have addressed the origins of phenotypic differences between fly species, we are still lacking a quantitative assessment of the variability in the way different fly species behave. We tackled this question in one of the most robust behaviors displayed by Drosophila: chemotaxis. At the larval stage, Drosophila melanogaster navigate odor gradients by combining four sensorimotor routines in a multilayered algorithm: a modulation of the overall locomotor speed and turn rate; a bias in turning during down-gradient motion; a bias in turning toward the gradient; the local curl of trajectories toward the gradient ("weathervaning"). Using high-resolution tracking and behavioral quantification, we characterized the olfactory behavior of eight closely related species of the Drosophila group in response to 19 ecologically-relevant odors. Significant changes are observed in the receptive field of each species, which is consistent with the rapid evolution of the peripheral olfactory system. Our results reveal substantial inter-species variability in the algorithms directing larval chemotaxis. While the basic sensorimotor routines are shared, their parametric arrangements can vary dramatically across species. The present analysis sets the stage for deciphering the evolutionary relationships between the structure and function of neural circuits directing orientation behaviors in Drosophila.

scholarly journals The ESAT-6/CFP-10 secretion system of Mycobacterium marinum modulates phagosome maturation

2006 ◽  
Vol 8 (9) ◽  
pp. 1417-1429 ◽  
Author(s):  
Tracy Tan ◽  
Warren L. Lee ◽  
David C. Alexander ◽  
Sergio Grinstein ◽  
Jun Liu
Keyword(s):  
Secretion System ◽  
Mycobacterium Marinum ◽  
Phagosome Maturation

scholarly journals Rab GTPases in Osteoclastic Bone Resorption and Autophagy

2020 ◽  
Vol 21 (20) ◽  
pp. 7655
Author(s):  
Michèle Roy ◽  
Sophie Roux
Keyword(s):  
Bone Resorption ◽  
Molecular Mechanisms ◽  
Bone Diseases ◽  
Vesicular Trafficking ◽  
Disease Development ◽  
Rab Gtpases ◽  
Bone Homeostasis ◽  
Autophagic Degradation ◽  
Ruffled Border ◽  
And Function

Small guanosine triphosphate hydrolases (GTPases) of the Rab family are involved in plasma membrane delivery, fusion events, and lysosomal and autophagic degradation pathways, thereby regulating signaling pathways and cell differentiation and function. Osteoclasts are bone-resorbing cells that maintain bone homeostasis. Polarized vesicular trafficking pathways result in the formation of the ruffled border, the osteoclast’s resorptive organelle, which also assists in transcytosis. Here, we reviewed the different roles of Rab GTPases in the endomembrane machinery of osteoclasts and in bone diseases caused by the dysfunction of these proteins, with a particular focus on autophagy and bone resorption. Understanding the molecular mechanisms underlying osteoclast-related bone disease development is critical for developing and improving therapies.

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