RAB31 marks and controls an ESCRT-independent exosome pathway

Wei, Denghui; Zhan, Weixiang; Gao, Ying; Huang, Liyan; Gong, Run; Wang, Wen; Zhang, Ruhua; Wu, Yuanzhong; Gao, Song; Kang, Tiebang

doi:10.1038/s41422-020-00409-1

Cited by 263 publications

(267 citation statements)

References 82 publications

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“…Another ESCRT-independent pathway involves active Ras-related protein, Rab31, and the formation of ILVs and exosomes while MVE degradation is avoided [42]. When Rab31 concentration is high in late endosomes, it can encounter active epidermal growth factor receptor (EGFR) which, in turn, activates Rab31 via tyrosine phosphorylation.…”

Section: Box 2: Extracellular Vesicle Biogenesis -Escrt-independent Pmentioning

confidence: 99%

Extracellular vesicles and intercellular communication in the central nervous system

Lizarraga-Valderrama

Sheridan

2021

FEBS Letters

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Neurons and glial cells of the central nervous system (CNS) release extracellular vesicles (EVs) to the interstitial fluid of the brain and spinal cord parenchyma. EVs contain proteins, nucleic acids and lipids that can be taken up by, and modulate the behaviour of, neighbouring recipient cells. The functions of EVs have been extensively studied in the context of neurodegenerative diseases. However, mechanisms involved in EV-mediated neuron-glial communication under physiological conditions or healthy ageing remain unclear. A better understanding of the myriad roles of EVs in CNS homeostasis is essential for the development of novel therapeutics to alleviate and reverse neurological disturbances of ageing. Proteomic studies are beginning to reveal cell type-specific EV cargo signatures that may one day allow us to target specific neuronal or glial cell populations in the treatment of debilitating neurological disorders. This review aims to synthesise the current literature regarding EV-mediated cell-cell communication in the brain, predominantly under physiological conditions.

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Section: Box 2: Extracellular Vesicle Biogenesis -Escrt-independent Pmentioning

confidence: 99%

Extracellular vesicles and intercellular communication in the central nervous system

Lizarraga-Valderrama

Sheridan

2021

FEBS Letters

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“…Aligning with this idea, EGFR signaling has been implicated in the formation of a subtype of very large (1-10 μm) membrane-derived microvesicles termed large oncosomes in prostate cancer cells [27] . Recently, constitutive active EGFR mutants have been found to drive their own secretion by promoting the production of a Rab31 dependent exosome subpopulation [28] . Mechanistically, active EGFR phosphorylates Rab31 on late endosomes, which in turn drives flotillin-dependent ILV formation.…”

Section: Oncogenes and Tumor Suppressors Governing Ev Secretionmentioning

confidence: 99%

The forces driving cancer extracellular vesicle secretion

et al. 2021

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The discovery that cancer cells discharge vast quantities of extracellular vesicles (EVs), underscored the explosion of the EV field. A large body of evidence now supports their onco-functionality in an array of contexts; stromal crosstalk, immune evasion, metastatic site priming, and drug resistance - justifying therapeutic intervention. The current bottleneck is a lack of clear understanding of why and how EV biogenesis ramps up in cancer cells, and hence where exactly avenues for intervention may reside. We know that EVs also play an array of physiological roles, therefore effective anticancer inhibition requires a target distinct enough from physiology to achieve efficacy. Taking the perspective that EV upregulation may be a consequence of the tumor landscape, we examine classic mutational events and tumor characteristics for EV regulators. All the while, aiming to illuminate topics worth further research in therapeutic development.

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“…Passive exosome formation involves the participation of lipids (ceramide), tetraspanins (CD63), and heat shock proteins independently of ESCRT [ 59 , 60 , 61 ]. Studies have shown localization of lipid metabolizing enzyme sphingomyelinase (SMase) and phospholipase D2 (PLD2) to MVB membrane induces the inward curvature required for exosome formation [ 62 , 63 , 64 ].…”

Section: Biogenesismentioning

confidence: 99%

Expedition into Exosome Biology: A Perspective of Progress from Discovery to Therapeutic Development

Jan

Rahman

Badierah

et al. 2021

Cancers

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Exosomes are membrane-enclosed distinct cellular entities of endocytic origin that shuttle proteins and RNA molecules intercellularly for communication purposes. Their surface is embossed by a huge variety of proteins, some of which are used as diagnostic markers. Exosomes are being explored for potential drug delivery, although their therapeutic utilities are impeded by gaps in knowledge regarding their formation and function under physiological condition and by lack of methods capable of shedding light on intraluminal vesicle release at the target site. Nonetheless, exosomes offer a promising means of developing systems that enable the specific delivery of therapeutics in diseases like cancer. This review summarizes information on donor cell types, cargoes, cargo loading, routes of administration, and the engineering of exosomal surfaces for specific peptides that increase target specificity and as such, therapeutic delivery.

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RAB31 marks and controls an ESCRT-independent exosome pathway

Cited by 263 publications

References 82 publications

Extracellular vesicles and intercellular communication in the central nervous system

Extracellular vesicles and intercellular communication in the central nervous system

The forces driving cancer extracellular vesicle secretion

Expedition into Exosome Biology: A Perspective of Progress from Discovery to Therapeutic Development

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