Biogenesis and function of ESCRT-dependent extracellular vesicles

Juan, Thomas; Fürthauer, Maximilian

doi:10.1016/j.semcdb.2017.08.022

Cited by 343 publications

(284 citation statements)

References 160 publications

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“…ILVs carry cargo into the lumen of late endosomes, where they can either be degraded if the late endosome fuses with the vacuole/lysosome (Frankel & Audhya 2018) or be released from the cell as exosomes if the endosome fuses with the plasma membrane (Jackson et al 2017, Juan & Fürthauer 2018) (Figure 1 a ). ILVs are small (~25–30 nm in diameter), and their bud necks are narrow (<10 nm).…”

Section: The Escrt Pathwaymentioning

confidence: 99%

Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes

McCullough

Frost

Sundquist

2018

Annu. Rev. Cell Dev. Biol.

232

272

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The endosomal sorting complexes required for transport (ESCRT) pathway mediates cellular membrane remodeling and fission reactions. The pathway comprises five core complexes: ALIX, ESCRT-I, ESCRT-II, ESCRT-III, and Vps4. These soluble complexes are typically recruited to target membranes by site-specific adaptors that bind one or both of the early-acting ESCRT factors: ALIX and ESCRT-I/ESCRT-II. These factors, in turn, nucleate assembly of ESCRT-III subunits into membrane-bound filaments that recruit the AAA ATPase Vps4. Together, ESCRT-III filaments and Vps4 remodel and sever membranes. Here, we review recent advances in our understanding of the structures, activities, and mechanisms of the ESCRT-III and Vps4 machinery, including the first high-resolution structures of ESCRT-III filaments, the assembled Vps4 enzyme in complex with an ESCRT-III substrate, the discovery that ESCRT-III/Vps4 complexes can promote both inside-out and outside-in membrane fission reactions, and emerging mechanistic models for ESCRT-mediated membrane fission.

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Section: The Escrt Pathwaymentioning

confidence: 99%

Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes

McCullough

Frost

Sundquist

2018

Annu. Rev. Cell Dev. Biol.

232

272

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“…MicroRNA loading into EVs occurs most likely during the formation of these EVs (Janas, Janas, Sapoń, & Janas, ; Juan & Furthauer, ; Mathiyalagan & Sahoo, ; Villarroya‐Beltri et al., ). EVs can be formed in different ways from the cell that produces them (Abels & Breakefield, ; Dreyer & Baur, ; Hessvik & Llorente, ; Juan & Furthauer, ; Rashed et al., ).…”

Section: Milk Micrornas In Health and Diseasementioning

confidence: 99%

Milk MicroRNAs in Health and Disease

Benmoussa

Provost

2019

Comp Rev Food Sci Food Safe

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MicroRNAs are small noncoding RNAs responsible for regulating 40% to 60% of gene expression at the posttranscriptional level. The discovery of circulating microRNAs in several biological fluids opened the path for their study as biomarkers and long‐range cell‐to‐cell communication mediators. Their transfer between individuals in the case of blood transfusion, for example, and their high enrichment in milk have sparked the interest for microRNA transfer through diet, especially from mothers to infants during breastfeeding. The extension of such paradigm led to the study of milk microRNAs in the case of cow or goat milk consumption in adults. Here we provide a comprehensive critical review of the key findings surrounding milk microRNAs in human, cow, and goat milk among other species. We discuss the data on their biological properties, their use as disease biomarkers, their transfer between individuals or species, and their putative or verified functions in health and disease of infants and adult consumers. This work is based on all the literature available and integrates all the results, theories, debates, and validation studies available so far on milk microRNAs and related areas of investigations. We critically discuss the limitations and outline future aspects and avenues to explore in this rapidly growing field of research that could impact public health through infant milk formulations or new therapies. We hope that this comprehensive review of the literature will provide insight for all teams investigating milk RNAs’ biological activities and help ensure the quality of future reports.

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“…1A). It is assumed that there are two different pathways leading to exosome formation, endosomal sorting complex required for transport (ESCRT)-dependent and independent (Colombo et al, 2013; Colombo, Raposo, & Thery, 2014; Hurley, 2015; Hurley & Odorizzi, 2012; Juan & Furthauer, 2017; Kowal, Tkach, & Thery, 2014; Marsh & van Meer, 2008; Stoorvogel, 2015; Trajkovic et al, 2008; Villarroya-Beltri, Baixauli, Gutierrez-Vazquez, Sanchez-Madrid, & Mittelbrunn, 2014). ESCRT proteins such as Alix 1 and TSG 101 form a neck-shaped complex with other proteins such as vacuolar sorting associated protein 4 (VPS4) initiating budding of exosomes at the MVE membrane.…”

Section: Got Exosomes: What’s (Really) In Your Prep?mentioning

confidence: 99%

Ceramide and Exosomes: A Novel Target in Cancer Biology and Therapy

Elsherbini

Bieberich

2018

Advances in Cancer Research

118

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Exosomes are secreted extracellular vesicles (EVs) that carry micro RNAs and other factors to reprogram cancer cells and tissues affected by cancer. Exosomes are exchanged between cancer cells and other tissues, often to prepare a premetastatic niche, escape immune surveillance, or spread multidrug resistance. Only a few studies investigated the function of lipids in exosomes, although their lipid composition is different from that of the secreting cells. Ceramide is one of the lipids critical for exosome formation and it is also enriched in these EVs. New research suggests that lipids in the exosomal membrane may organize and transmit “mobile rafts” that turn exosomes into extracellular signalosomes spreading activation of cell signaling pathways in oncogenesis and metastasis. Ceramide may modulate the function of mobile rafts and their effect on these cell signaling pathways. The critical role of lipids and in particular, ceramide for formation, secretion, and function of exosomes may lead to a radically new understanding of cancer biology and therapy.

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Biogenesis and function of ESCRT-dependent extracellular vesicles

Cited by 343 publications

References 160 publications

Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes

Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes

Milk MicroRNAs in Health and Disease

Ceramide and Exosomes: A Novel Target in Cancer Biology and Therapy

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