ArticleActa neuropathologica2015
Extracellular vesicle sorting of α-Synuclein is regulated by sumoylation.
Article in Acta neuropathologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed.
- Review
- Review
- From Mitochondria to Immunity: The Emerging Roles of Mitochondria-Derived Vesicles and Small Extracellular Vesicles in Cellular Communication and Disease.Journal of extracellular vesicles · 2025Review
- Extracellular Vesicles in Arthropods: Biogenesis, Functions, Isolation Methods and Applications.Journal of extracellular vesicles · 2025Review
- Screening, identification, and experimental validation of SUMOylation biomarkers in Parkinson's disease.Hereditas · 2025Article
- Extracellular vesicles: cargo loading, degradation and secretory pathways, and their intersection with autophagy.Extracellular vesicles and circulating nucleic acids · 2025Review
- Examination of the enrichment of neuronal extracellular vesicles from cell conditioned media and human plasma using an anti-NCAM immunocapture bead approach.BMC methods · 2025Article
- Posttranslational Modifications ofPharmacological reviews · 2024Review
- Current insights and assumptions on α-synuclein in Lewy body disease.Acta neuropathologica · 2024Review
- Extracellular Vesicles and Hydrogels: An Innovative Approach to Tissue Regeneration.ACS omega · 2024Review
- Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases.Neuroscience bulletin · 2024Review
- Extracellular Vesicles as Biomarkers for Parkinson's Disease: How Far from Clinical Translation?International journal of molecular sciences · 2024Review
- TRIM25 dictates selective miRNA loading into extracellular vesicles during inflammation.Scientific reports · 2023Article
- Paralogue-Specific Roles of SUMO1 and SUMO2/3 in Protein Quality Control and Associated Diseases.Cells · 2023Review
- A Review Study of the Participation of Late Domains in Sorting and Transport of Viral Factors to Exosomes.Life (Basel, Switzerland) · 2023Review
- Mechanisms of axonal support by oligodendrocyte-derived extracellular vesicles.Nature reviews. Neuroscience · 2023Review
- Exploiting the biogenesis of extracellular vesicles for bioengineering and therapeutic cargo loading.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- SUMO1 hinders α-Synuclein fibrillation by inducing structural compaction.Protein science : a publication of the Protein Society · 2023Article
- A shared fate for nuclear and cytosolic inclusions.Nature cell biology · 2023Article
- Ubiquitin and its relatives as wizards of the endolysosomal system.Journal of cell science · 2023Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors.
Funding
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Abstract
Extracellular α-Synuclein has been implicated in interneuronal propagation of disease pathology in Parkinson's Disease. How α-Synuclein is released into the extracellular space is still unclear. Here, we show that α-Synuclein is present in extracellular vesicles in the central nervous system. We find that sorting of α-Synuclein in extracellular vesicles is regulated by sumoylation and that sumoylation acts as a sorting factor for targeting of both, cytosolic and transmembrane proteins, to extracellular vesicles. We provide evidence that the SUMO-dependent sorting utilizes the endosomal sorting complex required for transport (ESCRT) by interaction with phosphoinositols. Ubiquitination of cargo proteins is so far the only known determinant for ESCRT-dependent sorting into the extracellular vesicle pathway. Our study reveals a function of SUMO protein modification as a Ubiquitin-independent ESCRT sorting signal, regulating the extracellular vesicle release of α-Synuclein. We deciphered in detail the molecular mechanism which directs α-Synuclein into extracellular vesicles which is of highest relevance for the understanding of Parkinson's disease pathogenesis and progression at the molecular level. We furthermore propose that sumo-dependent sorting constitutes a mechanism with more general implications for cell biology.
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