Mechanisms governing autophagosome biogenesis

Nature Reviews Molecular Cell Biology, Год журнала: 2020, Номер 21(8), С. 439 - 458

Опубликована: Май 5, 2020

Язык: Английский

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Exosomes as a new frontier of cancer liquid biopsy

Molecular Cancer, Год журнала: 2022, Номер 21(1)

Опубликована: Фев. 18, 2022

Abstract Liquid biopsy, characterized by minimally invasive detection through biofluids such as blood, saliva, and urine, has emerged a revolutionary strategy for cancer diagnosis prognosis prediction. Exosomes are subset of extracellular vesicles (EVs) that shuttle molecular cargoes from donor cells to recipient play crucial role in mediating intercellular communication. Increasing studies suggest exosomes have great promise serve novel biomarkers liquid since large quantities enriched body fluids involved numerous physiological pathological processes. However, the further clinical application been greatly restrained lack high-quality separation component analysis methods. This review aims provide comprehensive overview on conventional technologies exosome isolation, characterization content detection. Additionally, roles serving potential biopsy diagnosis, treatment monitoring, prediction summarized. Finally, prospects challenges applying exosome-based precision medicine evaluated.

Язык: Английский

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Exosomes as mediators of intercellular crosstalk in metabolism

Cell Metabolism, Год журнала: 2021, Номер 33(9), С. 1744 - 1762

Опубликована: Сен. 1, 2021

Язык: Английский

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Computed structures of core eukaryotic protein complexes

Science, Год журнала: 2021, Номер 374(6573)

Опубликована: Ноя. 11, 2021

Protein-protein interactions play critical roles in biology, but the structures of many eukaryotic protein complexes are unknown, and there likely not yet identified. We take advantage advances proteome-wide amino acid coevolution analysis deep-learning–based structure modeling to systematically identify build accurate models core within

Язык: Английский

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Machinery, regulation and pathophysiological implications of autophagosome maturation

Nature Reviews Molecular Cell Biology, Год журнала: 2021, Номер 22(11), С. 733 - 750

Опубликована: Июль 23, 2021

Язык: Английский

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Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer

Molecular Cancer, Год журнала: 2022, Номер 21(1)

Опубликована: Ноя. 1, 2022

Abstract Exosomes are well-known key mediators of intercellular communication and contribute to various physiological pathological processes. Their biogenesis involves four steps, including cargo sorting, MVB formation maturation, transport MVBs, fusion with the plasma membrane. Each process is modulated through competition or coordination multiple mechanisms, whereby diverse repertoires molecular cargos sorted into distinct subpopulations exosomes, resulting in high heterogeneity exosomes. Intriguingly, cancer cells exploit strategies, such as aberrant gene expression, posttranslational modifications, altered signaling pathways, regulate biogenesis, composition, eventually functions exosomes promote progression. Therefore, exosome biogenesis-targeted therapy being actively explored. In this review, we systematically summarize recent progress understanding machinery how it regulated context cancer. particular, highlight pharmacological targeting a promising therapeutic strategy.

Язык: Английский

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RAB31 marks and controls an ESCRT-independent exosome pathway

Cell Research, Год журнала: 2020, Номер 31(2), С. 157 - 177

Опубликована: Сен. 21, 2020

Abstract Exosomes are generated within the multivesicular endosomes (MVEs) as intraluminal vesicles (ILVs) and secreted during fusion of MVEs with cell membrane. The mechanisms exosome biogenesis remain poorly explored. Here we identify that RAB31 marks controls an ESCRT-independent pathway. Active RAB31, phosphorylated by epidermal growth factor receptor (EGFR), engages flotillin proteins in lipid raft microdomains to drive EGFR entry into form ILVs, which is independent ESCRT (endosomal sorting complex required for transport) machinery. interacts SPFH domain drives ILV formation via Flotillin proteins. Meanwhile, recruits GTPase-activating protein TBC1D2B inactivate RAB7, thereby preventing lysosomes enabling secretion ILVs exosomes. These findings establish has dual functions exosomes: driving suppressing degradation, providing exquisite framework better understand biogenesis.

Язык: Английский

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Shedding Light on Extracellular Vesicle Biogenesis and Bioengineering

Advanced Science, Год журнала: 2020, Номер 8(1)

Опубликована: Ноя. 27, 2020

Abstract Extracellular vesicles (EVs) are biocompatible, nano‐sized secreted containing many types of biomolecules, including proteins, RNAs, DNAs, lipids, and metabolites. Their low immunogenicity ability to functionally modify recipient cells by transferring diverse bioactive constituents make them an excellent candidate for a next‐generation drug delivery system. Here, the recent advances in EV biology emerging strategies bioengineering summarized, prospects clinical translation bioengineered EVs challenges be overcome discussed.

Язык: Английский

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Autophagosome biogenesis: From membrane growth to closure

The Journal of Cell Biology, Год журнала: 2020, Номер 219(6)

Опубликована: Май 1, 2020

Autophagosome biogenesis involves de novo formation of a membrane that elongates to sequester cytoplasmic cargo and closes form double-membrane vesicle (an autophagosome). This process has remained enigmatic since its initial discovery >50 yr ago, but our understanding the mechanisms involved in autophagosome increased substantially during last 20 yr. Several key questions do remain open, however, including, What determines site nucleation? is origin lipid composition membrane? How sequestration regulated under nonselective selective types autophagy? review provides insight into core molecular underlying biogenesis, with specific emphasis on modeling events, highlights recent conceptual advances field.

Язык: Английский

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Microautophagy – distinct molecular mechanisms handle cargoes of many sizes

Journal of Cell Science, Год журнала: 2020, Номер 133(17)

Опубликована: Сен. 1, 2020

ABSTRACT Autophagy is fundamental for cell and organismal health. Two types of autophagy are conserved in eukaryotes: macroautophagy microautophagy. During macroautophagy, autophagosomes deliver cytoplasmic constituents to endosomes or lysosomes, whereas during microautophagy lytic organelles take up cytoplasm directly. While has been investigated extensively, received much less attention. Nonetheless, it become clear that a broad range functions biosynthetic transport, metabolic adaptation, organelle remodeling quality control. This Review discusses the selective non-selective microautophagic processes known yeast, plants animals. Based on molecular mechanisms uptake cargo into organelles, I propose distinguish between fission-type microautophagy, which depends ESCRT proteins, fusion-type requires core machinery SNARE proteins. Many questions remain be explored, but functional versatility mechanistic diversity beginning emerge.

Язык: Английский

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