Assessment of Vault Particles in Cancer Cell Line‐Derived Extracellular Vesicle Preparations

ABSTRACT Extracellular vesicles (EVs) may contain a variety of molecular cargo, including proteins and nucleic acids. Vault particle components have been repeatedly reported in the literature as EV cargo. Here, we demonstrated that vault RNA (vtRNA) and major vault protein (MVP) were highly abundant...

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Main Authors: Xinming Liu, Zubair Ahmed Nizamudeen, Christopher J. Hill, Christopher Parmenter, Kenton P. Arkill, Daniel W. Lambert, Stuart Hunt
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Journal of Extracellular Vesicles
Subjects:
Online Access:https://doi.org/10.1002/jev2.70142
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author Xinming Liu
Zubair Ahmed Nizamudeen
Christopher J. Hill
Christopher Parmenter
Kenton P. Arkill
Daniel W. Lambert
Stuart Hunt
author_facet Xinming Liu
Zubair Ahmed Nizamudeen
Christopher J. Hill
Christopher Parmenter
Kenton P. Arkill
Daniel W. Lambert
Stuart Hunt
author_sort Xinming Liu
collection DOAJ
description ABSTRACT Extracellular vesicles (EVs) may contain a variety of molecular cargo, including proteins and nucleic acids. Vault particle components have been repeatedly reported in the literature as EV cargo. Here, we demonstrated that vault RNA (vtRNA) and major vault protein (MVP) were highly abundant in EV pellets enriched by differential centrifugation (DC) by qPCR and western blotting, respectively. RNase and proteinase treatment of DC‐derived pellets demonstrated that most vtRNA and MVP were not enclosed and protected within an EV membrane. Vault‐like particles were visualised in 100k DC pellets by cryo‐transmission electron microscopy. EVs were enriched by size exclusion chromatography, and western blotting of individual fractions showed co‐elution of EV markers and vault particle proteins. Immunocapture of EVs post‐ultracentrifugation (100k DC pellet) showed co‐purification of MVP, whereas EVs isolated by direct immunocapture from conditioned medium were MVP‐negative. The current study highlights the importance of determining the topology of putative EV‐associated components to determine if they are EV cargo or contaminants that have been co‐purified.
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language English
publishDate 2025-08-01
publisher Wiley
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series Journal of Extracellular Vesicles
spelling doaj-art-cfffd9a2c5f7429e81eb34db1a3dee192025-08-26T07:24:44ZengWileyJournal of Extracellular Vesicles2001-30782025-08-01148n/an/a10.1002/jev2.70142Assessment of Vault Particles in Cancer Cell Line‐Derived Extracellular Vesicle PreparationsXinming Liu0Zubair Ahmed Nizamudeen1Christopher J. Hill2Christopher Parmenter3Kenton P. Arkill4Daniel W. Lambert5Stuart Hunt6School of Clinical Dentistry The University of Sheffield Sheffield UKTranslational Medical Sciences, The University of Nottingham Biodiscovery Institute The University of Nottingham Nottingham UKCryo‐Electron Microscopy Facility The University of Sheffield Sheffield UKNanoscale and Microscale Research Centre The University of Nottingham Nottingham UKTranslational Medical Sciences, The University of Nottingham Biodiscovery Institute The University of Nottingham Nottingham UKSchool of Clinical Dentistry The University of Sheffield Sheffield UKSchool of Clinical Dentistry The University of Sheffield Sheffield UKABSTRACT Extracellular vesicles (EVs) may contain a variety of molecular cargo, including proteins and nucleic acids. Vault particle components have been repeatedly reported in the literature as EV cargo. Here, we demonstrated that vault RNA (vtRNA) and major vault protein (MVP) were highly abundant in EV pellets enriched by differential centrifugation (DC) by qPCR and western blotting, respectively. RNase and proteinase treatment of DC‐derived pellets demonstrated that most vtRNA and MVP were not enclosed and protected within an EV membrane. Vault‐like particles were visualised in 100k DC pellets by cryo‐transmission electron microscopy. EVs were enriched by size exclusion chromatography, and western blotting of individual fractions showed co‐elution of EV markers and vault particle proteins. Immunocapture of EVs post‐ultracentrifugation (100k DC pellet) showed co‐purification of MVP, whereas EVs isolated by direct immunocapture from conditioned medium were MVP‐negative. The current study highlights the importance of determining the topology of putative EV‐associated components to determine if they are EV cargo or contaminants that have been co‐purified.https://doi.org/10.1002/jev2.70142extracellular vesiclesmajor vault proteinvault particlevault RNA
spellingShingle Xinming Liu
Zubair Ahmed Nizamudeen
Christopher J. Hill
Christopher Parmenter
Kenton P. Arkill
Daniel W. Lambert
Stuart Hunt
Assessment of Vault Particles in Cancer Cell Line‐Derived Extracellular Vesicle Preparations
Journal of Extracellular Vesicles
extracellular vesicles
major vault protein
vault particle
vault RNA
title Assessment of Vault Particles in Cancer Cell Line‐Derived Extracellular Vesicle Preparations
title_full Assessment of Vault Particles in Cancer Cell Line‐Derived Extracellular Vesicle Preparations
title_fullStr Assessment of Vault Particles in Cancer Cell Line‐Derived Extracellular Vesicle Preparations
title_full_unstemmed Assessment of Vault Particles in Cancer Cell Line‐Derived Extracellular Vesicle Preparations
title_short Assessment of Vault Particles in Cancer Cell Line‐Derived Extracellular Vesicle Preparations
title_sort assessment of vault particles in cancer cell line derived extracellular vesicle preparations
topic extracellular vesicles
major vault protein
vault particle
vault RNA
url https://doi.org/10.1002/jev2.70142
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AT christopherjhill assessmentofvaultparticlesincancercelllinederivedextracellularvesiclepreparations
AT christopherparmenter assessmentofvaultparticlesincancercelllinederivedextracellularvesiclepreparations
AT kentonparkill assessmentofvaultparticlesincancercelllinederivedextracellularvesiclepreparations
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