Post-translational add-ons mark the path in exosomal protein sorting

Moreno-Gonzalo, Olga; Fernández-Delgado, Irene; Sánchez‐Madrid, Francisco

doi:10.1007/s00018-017-2690-y

Cited by 92 publications

(80 citation statements)

References 191 publications

(298 reference statements)

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“…More specifically, when comparing biological and functional significance of these alterations in the proteome profiles between M‐NVs and exosomes based on GO analyses, changes in translation, RNA processing, mRNA splicing, mitochondrial function, and protein transport to membrane were salient changes in M‐NVs (Figure C). MAPK signalling and functions associated with cell proliferation and protein folding, in addition PTMs were enriched in exosomes, and support the known literature of these components associated with exosomes biology …”

Section: Resultsmentioning

confidence: 99%

“…Based on significant enrichment of protein modification pathways in M‐NVs, and the important role protein modifications play in EV biology, including their roles in exosomes cargo sorting and trafficking, we performed unbiased mass spectrometry‐based protein (PTM) analysis of M‐NVs (Figure A). In brief, we investigated an informatic approach to identify PTM pattern changes with the requirement of select PTM enrichment that could be identified using discovery‐based proteomic data.…”

Section: Resultsmentioning

confidence: 99%

“…MAPK signalling and functions associated with cell proliferation and protein folding, in addition PTMs were enriched in exosomes, and support the known literature of these components associated with exosomes biology. [36][37][38] To identify enriched proteins present in M-NVs and exosomes, we performed statistical analysis on the expression levels of proteins identified in these datasets. We demonstrated 28 significantly enriched proteins in exosomes and 33 significantly enriched proteins in M-NVs (Figure 5).…”

Section: M-nvs Proteome Is Distinct From Exosomesmentioning

confidence: 99%

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Proteomic and Post‐Translational Modification Profiling of Exosome‐Mimetic Nanovesicles Compared to Exosomes

et al. 2019

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Issues associated with upscaling exosome production for therapeutic use may be overcome through utilizing artificial exosomes. Cell‐derived mimetic nanovesicles (M‐NVs) are a potentially promising alternative to exosomes for clinical applicability, demonstrating higher yield without incumbent production and isolation issues. Although several studies have shown that M‐NVs have similar morphology, size and therapeutic potential compared to exosomes, comprehensive characterization and to what extent M‐NVs components mimic exosomes remain elusive. M‐NVs were generated through the extrusion of cells and proteomic profiling demonstrated an enrichment of proteins associated with membrane and cytosolic components. The proteomic data herein reveal a subset of proteins that are highly abundant in M‐NVs in comparison to exosomes. M‐NVs contain proteins that largely represent the parental cell proteome, whereas the profile of exosomal proteins highlight their endosomally derived origin. This advantage of M‐NVs alleviates the necessity of endosomal sorting of endogenous therapeutic proteins or RNA into exosomes. This study also highlights differences in protein post‐translational modifications among M‐NVs, as distinct from exosomes. Overall this study provides key insights into defining the proteome composition of M‐NVs as a distinct from exosomes, and the potential advantage of M‐NVs as an alternative nanocarrier when spontaneous endosomal sorting of therapeutics are limited.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: M-nvs Proteome Is Distinct From Exosomesmentioning

confidence: 99%

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Proteomic and Post‐Translational Modification Profiling of Exosome‐Mimetic Nanovesicles Compared to Exosomes

et al. 2019

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“…Various mechanisms have been implicated in the specific sorting of proteins into exosomes, including ESCRT (endosomal sorting complexes required for transport)‐dependent and independent systems, tetraspanins, and lipid‐dependent mechanisms . More recently, post‐translational modifications, specifically ubiquitin and ubiquitin‐like modifiers are postulated to alter exosomal protein activation and increase proteome diversity . Currently, however, protein sorting mechanisms are only partially understood; thus warranting further investigation as exosome composition will ultimately determine the outcome of cell–cell communication.…”

Section: Discussionmentioning

confidence: 99%

“…[48,49] More recently, post-translational modifications, specifically ubiquitin and ubiquitin-like modifiers are postulated to alter exosomal protein activation and increase proteome diversity. [50] Currently, however, protein sorting mechanisms are only partially understood; thus warranting further investigation as exosome composition will ultimately determine the outcome of cell-cell communication. A better understanding of this process, together with profiling the proteomic content of exosomes offers an exciting avenue to ultimately allow for more precise treatment tailed to the phenotypic heterogeneity within a breast tumor.…”

Section: Discussionmentioning

confidence: 99%

Breast Cancer‐Derived Exosomes Reflect the Cell‐of‐Origin Phenotype

et al. 2019

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A manner in which cells can communicate with each other is via secreted nanoparticles termed exosomes. These vesicles contain lipids, nucleic acids, and proteins, and are said to reflect the cell‐of‐origin. However, for the exosomal protein content, there is limited evidence in the literature to verify this statement. Here, proteomic assessment combined with pathway‐enrichment analysis is used to demonstrate that the protein cargo of exosomes reflects the epithelial/mesenchymal phenotype of secreting breast cancer cells. Given that epithelial‐mesenchymal plasticity is known to implicate various stages of cancer progression, the results suggest that breast cancer subtypes with distinct epithelial and mesenchymal phenotypes may be distinguished by directly assessing the protein content of exosomes. Additionally, the work is a substantial step toward verifying the statement that cell‐derived exosomes reflect the phenotype of the cells‐of‐origin.

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RNA and Protein Delivery by Cell‐Secreted and Bioengineered Extracellular Vesicles

Wang

Luo

Vunjak-Novakovic

2021

Adv Healthcare Materials

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Extracellular vesicles (EVs) are carriers of biological signals through export and delivery of RNAs and proteins. Of increasing interest is the use of EVs as a platform for delivery of biomolecules. Preclinical studies have effectively used EVs to treat a number of diseases. Uniquely, endogenous machinery within cells can be manipulated in order to produce desirable loading of cargo within secreted EVs. In order to inform the development of such approaches, an understanding of the cellular mechanisms by which cargo is sorted to EVs is required. Here, the current knowledge of cargo sorting within EVs is reviewed. Here is given an overview of recent bioengineering approaches that leverage these advances. Methods of externally manipulating EV cargo are also discussed. Finally, a perspective on the current challenges of EVs as a drug delivery platform is offered. It is proposed that standardized bioengineering methods for therapeutic EV preparation will be required to create a well-defined clinical product.

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Post-translational add-ons mark the path in exosomal protein sorting

Cited by 92 publications

References 191 publications

Proteomic and Post‐Translational Modification Profiling of Exosome‐Mimetic Nanovesicles Compared to Exosomes

Proteomic and Post‐Translational Modification Profiling of Exosome‐Mimetic Nanovesicles Compared to Exosomes

Breast Cancer‐Derived Exosomes Reflect the Cell‐of‐Origin Phenotype

RNA and Protein Delivery by Cell‐Secreted and Bioengineered Extracellular Vesicles

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