The different roles of V-ATPase a subunits in phagocytosis/endocytosis and autophagy DOI
Qi Chen,

H. Kou,

Doris Lou Demy

et al.

Autophagy, Journal Year: 2024, Volume and Issue: 20(10), P. 2297 - 2313

Published: June 14, 2024

Microglia are specialized macrophages responsible for the clearance of dead neurons and pathogens by phagocytosis degradation. The degradation requires phagosome maturation acidification provided vesicular- or vacuolar-type H+-translocating adenosine triphosphatase (V-ATPase), which is composed cytoplasmic V1 domain membrane-embedded Vo domain. V-ATPase a subunit, an integral part domain, has four isoforms in mammals. functions different on cells/species remain controversial. Here we show that mutations both Atp6v0a1 Tcirg1b/Atp6v0a3 subunits lead to accumulation phagosomes zebrafish microglia. However, their mechanisms different. subunit mainly distributed early late phagosomes. Defects this defective transition from In contrast, primarily located lysosomes regulates phagosome-lysosomal fusion. Defective Tcirg1b/Atp6v0a3, but not leads reduced impaired macroautophagy/autophagy We further showed ATP6V0A1/a1 TCIRG1/a3 mouse preferentially endosomes lysosomes, respectively. Blocking these disrupted early-to-late endosome endosome-to-lysosome fusion, Taken together, our results highlight essential conserved roles played multiple steps endocytosis across various species.

Language: Английский

OpenCell: Endogenous tagging for the cartography of human cellular organization DOI
Nathan Cho, Keith C. Cheveralls, Andreas‐David Brunner

et al.

Science, Journal Year: 2022, Volume and Issue: 375(6585)

Published: March 10, 2022

Elucidating the wiring diagram of human cell is a central goal postgenomic era. We combined genome engineering, confocal live-cell imaging, mass spectrometry, and data science to systematically map localization interactions proteins. Our approach provides data-driven description molecular spatial networks that organize proteome. Unsupervised clustering these delineates functional communities facilitate biological discovery. found remarkably precise information can be derived from protein patterns, which often contain enough identify interactions, RNA binding proteins form specific subgroup defined by unique interaction properties. Paired with fully interactive website (opencell.czbiohub.org), our work constitutes resource for quantitative cartography cellular organization.

Language: Английский

Citations

368
Molecular basis of V-ATPase inhibition by bafilomycin A1 DOI Creative Commons
Rong Wang, Jin Wang, Abdirahman Hassan

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: March 19, 2021

Abstract Pharmacological inhibition of vacuolar-type H + -ATPase (V-ATPase) by its specific inhibitor can abrogate tumor metastasis, prevent autophagy, and reduce cellular signaling responses. Bafilomycin A1, a member macrolide antibiotics an autophagy inhibitor, serves as potent V-ATPases inhibitor. Although there are many V-ATPase structures reported, the molecular basis inhibitors on remains unknown. Here, we report cryo-EM structure bafilomycin A1 bound intact bovine at overall resolution 3.6-Å. The reveals six molecules to c-ring. One molecule engages with two c subunits disrupts interactions between c-ring subunit , thereby preventing proton translocation. Structural sequence analyses demonstrate that A1-binding residues conserved in yeast mammalian species 7’-hydroxyl group acts unique feature recognized .

Language: Английский

Citations

142
Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology DOI
Carmine Settembre, Rushika M. Perera

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 223 - 245

Published: Nov. 24, 2023

Language: Английский

Citations

88
Lysosomes in senescence and aging DOI
Xiaojun Tan, Toren Finkel

EMBO Reports, Journal Year: 2023, Volume and Issue: 24(11)

Published: Oct. 9, 2023

Language: Английский

Citations

47
High-resolution electron cryomicroscopy of V-ATPase in native synaptic vesicles DOI
Claire E. Coupland, Ryan Karimi, Stephanie A. Bueler

et al.

Science, Journal Year: 2024, Volume and Issue: 385(6705), P. 168 - 174

Published: June 20, 2024

Intercellular communication in the nervous system occurs through release of neurotransmitters into synaptic cleft between neurons. In presynaptic neuron, proton pumping vesicular- or vacuolar-type ATPase (V-ATPase) powers neurotransmitter loading vesicles (SVs), with V 1 complex dissociating from membrane region enzyme before exocytosis. We isolated SVs rat brain using SidK, a V-ATPase–binding bacterial effector protein. Single-particle electron cryomicroscopy allowed high-resolution structure determination V-ATPase within native SV membrane. structure, regularly spaced cholesterol molecules decorate enzyme’s rotor and abundant protein synaptophysin binds stoichiometrically. ATP hydrolysis during vesicle results loss membrane, suggesting that is sufficient to induce dissociation enzyme.

Language: Английский

Citations

25
Chitosan-Based Drug Delivery System: Applications in Fish Biotechnology DOI Open Access
Yuanbing Wu, Ania Rashidpour, María Pilar Almajano

et al.

Polymers, Journal Year: 2020, Volume and Issue: 12(5), P. 1177 - 1177

Published: May 21, 2020

Chitosan is increasingly used for safe nucleic acid delivery in gene therapy studies, due to well-known properties such as bioadhesion, low toxicity, biodegradability and biocompatibility. Furthermore, chitosan derivatization can be easily performed improve the solubility stability of chitosan–nucleic polyplexes, enhance efficient target cell drug delivery, uptake, intracellular endosomal escape, unpacking nuclear import expression plasmids. As other fields, a promising vector with great potential fish farming industry. This review highlights state-of-the-art assays using chitosan-based methodologies delivering acids into cells, focuses attention on recent advances chitosan-mediated biotechnology applications. The efficiency studies discussed fields vaccination against bacterial viral infection, control gonadal development overexpression silencing overcoming metabolic limitations, dependence protein-rich diets glucose tolerance farmed fish. Finally, challenges perspectives future developments are also discussed.

Language: Английский

Citations

90
Built to last: lysosome remodeling and repair in health and disease DOI Creative Commons
Roberto Zoncu, Rushika M. Perera

Trends in Cell Biology, Journal Year: 2022, Volume and Issue: 32(7), P. 597 - 610

Published: Feb. 2, 2022

Language: Английский

Citations

52
The surface coating of iron oxide nanoparticles drives their intracellular trafficking and degradation in endolysosomes differently depending on the cell type DOI Creative Commons
Yadileiny Portilla, Vladimir Mulens‐Arias, Alberto Paradela

et al.

Biomaterials, Journal Year: 2022, Volume and Issue: 281, P. 121365 - 121365

Published: Jan. 6, 2022

Magnetic nanoparticles (MNPs) are potential theranostic tools that biodegraded through different endocytic pathways. However, little is known about the endolysosomal network which MNPs transit and influence of surface coating in this process. Here, we studied intracellular two with identical iron oxide core size but distinct coatings: 3-aminopropyl-trietoxysilane (APS) dimercaptosuccinic acid (DMSA). Using markers a high throughput analysis associated proteome, tracked intracellularly mouse cell lines, RAW264.7 (macrophages) Pan02 (tumor cells). We did not detect differences MNP trafficking kinetics nor MNP-containing endolysosome phenotype cells. Nonetheless, DMSA-MNPs transited at slower rate than APS-MNPs macrophages as measured by accumulation Rab7+ endolysosomes. Macrophage DMSA-MNP-containing endolysosomes had higher percentage lytic enzymes catalytic proteins their APS-MNP counterparts, concomitantly V-type ATPase enrichment, suggesting an acidic nature. Consequently, more autophagic vesicles induced macrophages, enhancing expression metabolism-related genes proteins. Therefore, unlike cells, appears to nature macrophages. These results highlight how can determine nanoparticle fate biodegradation cell-type bias.

Language: Английский

Citations

39
Tumor cell membrane‐based vaccines: A potential boost for cancer immunotherapy DOI Creative Commons
Muyang Yang, Jie Zhou,

Liseng Lu

et al.

Exploration, Journal Year: 2024, Volume and Issue: 4(6)

Published: March 28, 2024

Abstract Because therapeutic cancer vaccines can, in theory, eliminate tumor cells specifically with relatively low toxicity, they have long been considered for application repressing progression. Traditional containing a single or few discrete epitopes failed the clinic, possibly due to challenges epitope selection, target downregulation, cell heterogeneity, microenvironment immunosuppression, lack of vaccine immunogenicity. Whole membrane vaccines, which provide rich source antigens, are emerging as viable alternatives. Autologous and allogenic cellular evaluated clinical treatments. Tumor membranes (TCMs) an intriguing antigen source, membrane‐accessible targets and, at same time, serve integrated carriers adjuvants other agents. This review provides summary properties technologies TCM vaccines. Characteristics, categories, mechanisms, preparation methods discussed, demonstrable additional benefits derived from combining chemotherapy, sonodynamic therapy, phototherapy, oncolytic viruses. Further research chemistry, biomedicine, immunology, bioinformatics address current drawbacks could facilitate adoption

Language: Английский

Citations

12
Conjugation of ATG8s to single membranes at a glance DOI Creative Commons
Carmen Figueras-Novoa,

Lewis Timimi,

Elena Marcassa

et al.

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(15)

Published: Aug. 1, 2024

Autophagy refers to a set of degradative mechanisms whereby cytoplasmic contents are targeted the lysosome. This is best described for macroautophagy, where double-membrane compartment (autophagosome) generated engulf contents. Autophagosomes decorated with ubiquitin-like ATG8 molecules (ATG8s), which recruited through covalent lipidation, catalysed by E3-ligase-like ATG16L1 complex. LC3 proteins family members that often used as marker autophagosomes. In contrast canonical conjugation ATG8s single membranes (CASM) describes group non-canonical autophagy processes in pre-existing single-membrane compartments. CASM occurs response disrupted intracellular pH gradients, when V-ATPase proton pump recruits process called V-ATPase-ATG16L1-induced lipidation (VAIL). Recent work has demonstrated parallel, alternative axis induction, triggered membrane recruitment factor TECPR1 recognises sphingomyelin exposed on cytosolic face and forms an sphingomyelin-TECPR1-induced (STIL) independent ATG16L1. light these discoveries, this Cell Science at Glance article summarises two highlight how they differ from each other.

Language: Английский

Citations

11