Journal article
Non-Vesicular Extracellular Particle (NVEP) Proteomes from Diverse Biological Sources Reveal Specific Marker Composition with Varying Enrichment Levels
Biomolecules (Basel, Switzerland), Vol.15(11), 1487
10/22/2025
DOI: 10.3390/biom15111487
PMCID: PMC12650339
PMID: 41301405
Abstract
Extracellular particles (EPs), an umbrella term encompassing membrane-enclosed extracellular vesicles (EVs) and non-vesicular extracellular particles ([NVEPs], previously described as extracellular condensates [ECs]) contain a complex cargo of biomolecules, including DNA, RNA, proteins, and lipids, reflecting the physiological state of their cell of origin. Identifying proteins associated with EPs that regulate host responses to physiological and pathophysiological processes is of critical importance. Here, we report the findings of our study to gain insight into the proteins associated with NVEPs. We used samples from human semen, the rat brain, and the rhesus macaque (RM) brain and blood to assess the physical properties and proteome profiles of NVEPs from these specimens. The results show significant differences in the zeta potential, concentration, and size of NVEPs across different species. We identified 938, 51, and 509 total proteins from NVEPs isolated from rat brain tissues, RM blood, and human seminal plasma, respectively. The species-specific protein networks show distinct biological themes, while the species-conserved protein interactome was identified with six proteins (ALB, CST3, FIBA/FGA, GSTP1, PLMN/PLG, PPIA) associated with NVEPs in all samples. The six NVEP-associated proteins are prone to aggregation and formation of wide, insoluble, unbranched filaments with a cross-beta sheet quaternary structure, such as amyloid fibrils. Protein-to-function analysis indicates that the six identified proteins are linked to the release of dopamine, immune-mediated inflammatory disease, replication of RNA viruses, HIV-HCV co-infection, and inflammation. These interesting findings have created an opportunity to evaluate NVEPs for their potential use as biomarkers of health and disease. Additional in-depth studies are needed to clarify when and how these proteins sustain their physiological role or transition to pathogenic roles.
Details
- Title: Subtitle
- Non-Vesicular Extracellular Particle (NVEP) Proteomes from Diverse Biological Sources Reveal Specific Marker Composition with Varying Enrichment Levels
- Creators
- Wasifa Naushad - New York Medical CollegeBryson C. Okeoma - New York Medical CollegeCarlos Gartner - MaineHealthYulica Santos-Ortega - MaineHealthCalvin P. H. Vary - University of MaineLakmini S. Premadasa - Texas Biomedical Research InstituteAlessio Noghero - Biomedical Research InstituteJack T. Stapleton - University of IowaIonita C. Ghiran - Beth Israel Deaconess Medical CenterMahesh Mohan - Texas Biomedical Research InstituteChioma M. Okeoma - New York Medical College
- Resource Type
- Journal article
- Publication Details
- Biomolecules (Basel, Switzerland), Vol.15(11), 1487
- DOI
- 10.3390/biom15111487
- PMID
- 41301405
- PMCID
- PMC12650339
- NLM abbreviation
- Biomolecules
- ISSN
- 2218-273X
- eISSN
- 2218-273X
- Publisher
- MDPI
- Grant note
- VA SeqCURE: BX000207 National Institutes of Health: R01DA042348-01, R01DA050169, R21/R33DA053643, S10OD 036364, P20GM121301, U54GM115516, 1S10OD028508 NYMC and Lovelace Biomedical
National Institutes of Health grant R01DA042348-01 (to CMO), National Institutes of Health grant R01DA050169 (to CMO and MM), National Institutes of Health grant R21/R33DA053643 (to CMO and MM), National Institutes of Health grant S10OD 036364 (to CMO), National Institutes of Health grants P20GM121301, U54GM115516 and 1S10OD028508 (to CPHV), VA Merit Review BX000207 and VA SeqCURE grant (to JTS), and startup funds from NYMC and Lovelace Biomedical.
- Language
- English
- Date published
- 10/22/2025
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9985017451602771
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