scholarly journals Maintenance and loss of endocytic organelle integrity: mechanisms and implications for antigen cross-presentation

Open Biology ◽  
2021 ◽  
Vol 11 (11) ◽  
Author(s):  
Eleanor Childs ◽  
Conor M. Henry ◽  
Johnathan Canton ◽  
Caetano Reis e Sousa
Keyword(s):  
Cell Biology ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Cross Presentation ◽  
Cellular Processes ◽  
Cell Responses ◽  
Intracellular Drug Delivery ◽  
Histocompatibility Complex ◽  
Repair Mechanisms ◽  
Organelle Membrane

The membranes of endosomes, phagosomes and macropinosomes can become damaged by the physical properties of internalized cargo, by active pathogenic invasion or by cellular processes, including endocytic maturation. Loss of membrane integrity is often deleterious and is, therefore, prevented by mitigation and repair mechanisms. However, it can occasionally be beneficial and actively induced by cells. Here, we summarize the mechanisms by which cells, in particular phagocytes, try to prevent membrane damage and how, when this fails, they repair or destroy damaged endocytic organelles. We also detail how one type of phagocyte, the dendritic cell, can deliberately trigger localized damage to endocytic organelles to allow for major histocompatibility complex class I presentation of exogenous antigens and initiation of CD8 + T-cell responses to viruses and tumours. Our review highlights mechanisms for the regulation of endocytic organelle membrane integrity at the intersection of cell biology and immunology that could be co-opted for improving vaccination and intracellular drug delivery.

scholarly journals Interdisciplinary Synergy to Reveal Mechanisms of Annexin-Mediated Plasma Membrane Shaping and Repair

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1029 ◽  
Author(s):  
Poul Martin Bendix ◽  
Adam Cohen Simonsen ◽  
Christoffer D. Florentsen ◽  
Swantje Christin Häger ◽  
Anna Mularski ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Biology ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Interdisciplinary Approach ◽  
Membrane Repair ◽  
Cell Membrane Integrity ◽  
Curvature Sensing ◽  
Plasma Membrane Repair ◽  
Curved Membranes

The plasma membrane surrounds every single cell and essentially shapes cell life by separating the interior from the external environment. Thus, maintenance of cell membrane integrity is essential to prevent death caused by disruption of the plasma membrane. To counteract plasma membrane injuries, eukaryotic cells have developed efficient repair tools that depend on Ca2+- and phospholipid-binding annexin proteins. Upon membrane damage, annexin family members are activated by a Ca2+ influx, enabling them to quickly bind at the damaged membrane and facilitate wound healing. Our recent studies, based on interdisciplinary research synergy across molecular cell biology, experimental membrane physics, and computational simulations show that annexins have additional biophysical functions in the repair response besides enabling membrane fusion. Annexins possess different membrane-shaping properties, allowing for a tailored response that involves rapid bending, constriction, and fusion of membrane edges for resealing. Moreover, some annexins have high affinity for highly curved membranes that appear at free edges near rupture sites, a property that might accelerate their recruitment for rapid repair. Here, we discuss the mechanisms of annexin-mediated membrane shaping and curvature sensing in the light of our interdisciplinary approach to study plasma membrane repair.

scholarly journals Non-canonical autophagy in dendritic cells restricts cross-presentation and anti-tumor immunity

2019 ◽  
Author(s):  
Payel Sil ◽  
Fei Zhao ◽  
Ginger W. Muse ◽  
Sing-Wai Wong ◽  
Joseph P. Kolb ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Molecular Mechanisms ◽  
Tumor Therapy ◽  
Tumor Burden ◽  
Mhc I ◽  
Cross Presentation ◽  
Cell Responses ◽  
Histocompatibility Complex ◽  
Novel Strategy ◽  
Gain Access

SummaryMajor Histocompatibility Complex I (MHC-I) molecules classically present peptides derived from endogenous antigens, but exogenous antigens can also gain access to the MHC-I machinery in dendritic cells (DCs), which can activate antigen-specific CD8+T cells. This process, termed cross-presentation, can be triggered by the uptake of dying autologous cells, including tumor cells, by DCs. The molecular mechanisms that underlie efficient cross-presentation remain largely uncharacterized, and an improved understanding of these mechanisms might reveal novel strategies for anti-tumor therapies. Rubicon (RUBCN) is a molecule required for LC3-associated phagocytosis (LAP), but dispensable for canonical autophagy, and mice lacking this protein develop an autoimmune inflammatory pathology with age. Here, we demonstrate thatRubcn-deficient DCs have increased retention of engulfed cellular cargo in immature phagosomes resulting in increased phagosome-to-cytosol escape and antigen access to proteasome-mediated degradation. As a result, mice selectively lackingRubcnin DCs mount stronger tumor antigen-specific CD8+T cell responses and exhibit decreased tumor burden compared to wild type littermates. These findings identify LAP as a key regulator of cross-presentation and suggest that targeting RUBCN might represent a novel strategy for anti-tumor therapy.

IMPACT OF SORBITOL- INDUCED OSMOTIC STRESS ON SOME BIOCHEMICAL TRAITS OF POTATO IN VITRO

2020 ◽  
Vol 51 (4) ◽  
pp. 1038-1047
Author(s):  
Mawia & et al.
Keyword(s):  
Ascorbic Acid ◽  
Osmotic Stress ◽  
Cytoplasmic Membrane ◽  
Genotypic Variation ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Culture Collection ◽  
Nutritive Medium ◽  
Starting Point

This study had as principal objective identification of osmotic-tolerant potato genotypes by using "in vitro" tissue culture and sorbitol as a stimulating agent, to induce water stress, which was added to the  culture nutritive medium in different concentration (0,50, 110, 220, 330 and 440 mM).  The starting point was represented by plantlets culture collection, belonging to eleven potato genotypes: Barcelona, Nectar, Alison, Jelly, Malice, Nazca, Toronto, Farida, Fabulla, Colomba and Spunta. Plantlets were multiplied between two internodes to obtain microcuttings (in sterile condition), which were inoculated on medium. Sorbitol-induced osmotic stress caused a significant reduction in the ascorbic acid, while the concentration of proline, H2O2 and solutes leakage increased compared with the control. Increased the proline content prevented lipid peroxidation, which played a pivotal role in the maintenance of membrane integrity under osmotic stress conditions. The extent of the cytoplasmic membrane damage depends on osmotic stress severity and the genotypic variation in the maintenance of membranes stability was highly associated with the ability of producing more amounts of osmoprotectants (proline) and the non-enzymic antioxidant ascorbic acid in response to osmotic stress level. The results showed that the genotypes Jelly, Nectar, Allison, Toronto, and Colomba are classified as highly osmotic stress tolerant genotypes, while the genotypes Nazca and Farida are classified as osmotic stress susceptible ones.

scholarly journals Plasma membrane integrity in health and disease: significance and therapeutic potential

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Catarina Dias ◽  
Jesper Nylandsted
Keyword(s):  
Plasma Membrane ◽  
Therapeutic Potential ◽  
Calcium Influx ◽  
Membrane Integrity ◽  
Cell Types ◽  
Physical Parameters ◽  
Membrane Repair ◽  
Plasma Membrane Integrity ◽  
Repair Mechanisms ◽  
And Function

AbstractMaintenance of plasma membrane integrity is essential for normal cell viability and function. Thus, robust membrane repair mechanisms have evolved to counteract the eminent threat of a torn plasma membrane. Different repair mechanisms and the bio-physical parameters required for efficient repair are now emerging from different research groups. However, less is known about when these mechanisms come into play. This review focuses on the existence of membrane disruptions and repair mechanisms in both physiological and pathological conditions, and across multiple cell types, albeit to different degrees. Fundamentally, irrespective of the source of membrane disruption, aberrant calcium influx is the common stimulus that activates the membrane repair response. Inadequate repair responses can tip the balance between physiology and pathology, highlighting the significance of plasma membrane integrity. For example, an over-activated repair response can promote cancer invasion, while the inability to efficiently repair membrane can drive neurodegeneration and muscular dystrophies. The interdisciplinary view explored here emphasises the widespread potential of targeting plasma membrane repair mechanisms for therapeutic purposes.

scholarly journals Plasma membrane integrity: implications for health and disease

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dustin A. Ammendolia ◽  
William M. Bement ◽  
John H. Brumell
Keyword(s):  
Plasma Membrane ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Whole Body ◽  
Plasma Membrane Integrity ◽  
Plasma Membrane Damage ◽  
Cellular Environment ◽  
Health And Disease ◽  
Repair Pathways ◽  
The Impact

AbstractPlasma membrane integrity is essential for cellular homeostasis. In vivo, cells experience plasma membrane damage from a multitude of stressors in the extra- and intra-cellular environment. To avoid lethal consequences, cells are equipped with repair pathways to restore membrane integrity. Here, we assess plasma membrane damage and repair from a whole-body perspective. We highlight the role of tissue-specific stressors in health and disease and examine membrane repair pathways across diverse cell types. Furthermore, we outline the impact of genetic and environmental factors on plasma membrane integrity and how these contribute to disease pathogenesis in different tissues.

scholarly journals Fluorescent Chitosan Nanogels Developed for Targeting Endothelial Cells of Axillary Lymph Nodes

2020 ◽  
Vol 4 (1) ◽  
pp. 12
Author(s):  
Miruna-Silvia Stan ◽  
Ionela Cristina Nica ◽  
Juliette Moreau ◽  
Maïté Callewaert ◽  
Cyril Cadiou ◽  
...  
Keyword(s):  
Membrane Damage ◽  
Membrane Integrity ◽  
Simian Virus 40 ◽  
Cancer Diagnostics ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Microvascular Endothelial Cell ◽  
Axillary Lymph Nodes ◽  
Cell Periphery ◽  
Axillary Lymph

Nanogels are a novel class of three-dimensional cross-linked polymers able to retain high amounts of water in their network structure, with large potential applications in nanomedicine. In our study, the polymer matrix selected was chitosan, as this polysaccharide biopolymer composed of N-acetylglucosamine and glucosamine residues exhibits great biocompatibility and low toxicity. The preparation was performed by ionic gelation in the presence of hyaluronic acid and sodium tripolyphosphate, with rhodamine or fluorescein isothiocyanate molecules grafted on a chitosan backbone. In order to validate the possible usage of these chitosan-fluorophores conjugates for fluorescence imaging purposes in cancer diagnostics and therapy, their biological effect was assessed on SVEC4-10 cells (a simian virus 40-transformed mouse microvascular endothelial cell line). Cell viability, membrane integrity and nanogels uptake were examined following exposure for 6 and 24 h at concentrations up to 120 µg/mL. A good biocompatibility was obtained after both time intervals of incubation with nanogels, with no increase in cell death or membrane damage being noticed as compared to control. By examination on confocal laser scanning microscopy, both types of fluorescent nanogels agglomerated on the surface of the cell membrane, their cellular internalization being observed only for few cells, preferentially at the cell periphery. In conclusion, based on the biocompatibility of the nanogels, these can further incorporate gadolinium for an improved magnetic resonance imaging effect in nanomedicine.

Hydraulic consequences of enzymatic breakdown of grapevine pit membranes

2021 ◽  
Author(s):  
Ana Clara Fanton ◽  
Craig Brodersen
Keyword(s):  
Hydraulic Conductivity ◽  
Vascular System ◽  
Membrane Surface ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Biological Response ◽  
Plant Host ◽  
Important Species ◽  
Membrane Area ◽  
Pit Membrane

Abstract Xylella fastidiosa (Xf) is the xylem-dwelling bacterial agent associated with Pierce’s Disease (PD), which leads to significant declines in productivity in agriculturally important species like grapevine (Vitis vinifera). Xf spreads through the xylem network by digesting the pit membranes between adjacent vessels, thereby potentially changing the hydraulic properties of the stem. However, the effects of Xf on water transport varies depending on the plant host and the infection stage, presenting diverse outcomes. Here, we investigated the effects of polygalacturonase, an enzyme known to be secreted by Xf when it produces biofilm on the pit membrane surface, on stem hydraulic conductivity and pit membrane integrity. Experiments were performed on six grapevine genotypes with varying levels of PD resistance, with the expectation that pit membrane resistance to degradation by polygalacturonase may play a role in PD-resistance. Our objective was to study a single component of this pathosystem in isolation to better understand the mechanisms behind reported changes in hydraulics, thereby excluding the biological response of the plant to the presence of Xf in the vascular system. Pit membrane damage only occurred in stems perfused with polygalacturonase. Although the damaged pit membrane area was small (2-9% of the total pit aperture area), membrane digestion led to significant changes in the median air-seeding thresholds, and most importantly, shifted frequency distribution. Finally, enzyme perfusion also resulted in a universal reduction in stem hydraulic conductivity, suggesting the development of tyloses may not be the only contributing factor to reduced hydraulic conductivity in infected grapevine.

scholarly journals WDFY4 is required for cross-presentation in response to viral and tumor antigens

Science ◽  
2018 ◽  
Vol 362 (6415) ◽  
pp. 694-699 ◽  
Author(s):  
Derek J. Theisen ◽  
Jesse T. Davidson ◽  
Carlos G. Briseño ◽  
Marco Gargaro ◽  
Elvin J. Lauron ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Tumor Antigens ◽  
Critical Role ◽  
Tumor Rejection ◽  
Interleukin 12 ◽  
Cross Presentation ◽  
Histocompatibility Complex ◽  
Crispr Screen

During the process of cross-presentation, viral or tumor-derived antigens are presented to CD8+ T cells by Batf3-dependent CD8α+/XCR1+ classical dendritic cells (cDC1s). We designed a functional CRISPR screen for previously unknown regulators of cross-presentation, and identified the BEACH domain–containing protein WDFY4 as essential for cross-presentation of cell-associated antigens by cDC1s in mice. However, WDFY4 was not required for major histocompatibility complex class II presentation, nor for cross-presentation by monocyte-derived dendritic cells. In contrast to Batf3–/– mice, Wdfy4–/– mice displayed normal lymphoid and nonlymphoid cDC1 populations that produce interleukin-12 and protect against Toxoplasma gondii infection. However, similar to Batf3–/– mice, Wdfy4–/– mice failed to prime virus-specific CD8+ T cells in vivo or induce tumor rejection, revealing a critical role for cross-presentation in antiviral and antitumor immunity.

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