ArticleProceedings of the National Academy of Sciences of the United States of America2020
A myosin-7B-dependent endocytosis pathway mediates cellular entry of α-synuclein fibrils and polycation-bearing cargos.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 57 citations in OpenAlex.
- Proteoglycans are protagonists in autophagy, lymphangiogenesis, and neurodegenerative diseases.Trends in cell biology · 2026Review
- Propagation of α-synuclein pathology: models, mechanisms and future goals.Molecular neurodegeneration advances · 2026Review
- Novel regulators of heparan sulfate proteoglycans modulate cellular uptake of α-synuclein fibrils.Communications biology · 2025Article
- Time-course remodeling and pathology intervention of α-synuclein amyloid fibril by heparin and heparin-like oligosaccharides.Nature structural & molecular biology · 2025Article
- Article
- [Plasma long noncoding RNA expression profiles in patients with Parkinson's disease and the role of lnc-CTSD-5:1 in a PD cell model: a ceRNA microarray-based study].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- A Rare Case of Polymicrogyria in an Elderly Individual With Unique Polygenic Underlining.Cureus · 2024Article
- Tilorone mitigates the propagation of α-synucleinopathy in a midbrain-like organoid model.Journal of translational medicine · 2024Article
- Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein.Nature communications · 2024Article
- Decoding the Cellular Trafficking of Prion-like Proteins in Neurodegenerative Diseases.Neuroscience bulletin · 2024Review
- Cell membrane proteome analysis in HEK293T cells challenged with α-synuclein amyloids.Journal of biosciences · 2024Article
- Emerging role of microglia in inter-cellular transmission of α-synuclein in Parkinson's disease.Frontiers in aging neuroscience · 2024Review
- Intercellular transmission of alpha-synuclein.Frontiers in molecular neuroscience · 2024Review
- Host heparan sulfate promotes ACE2 super-cluster assembly and enhances SARS-CoV-2-associated syncytium formation.Nature communications · 2023Article
- Heparan sulfate promotes ACE2 super-cluster assembly to enhance SARS-CoV-2-associated syncytium formation.Research square · 2023Article
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- Background and roles: myosin in autoimmune diseases.Frontiers in cell and developmental biology · 2023Review
- Review
- Heparin induces α-synuclein to form new fibril polymorphs with attenuated neuropathology.Nature communications · 2022Article
- Immunohistochemical Demonstration of the pGlu79 α-Synuclein Fragment in Alzheimer's Disease and Its Tg2576 Mouse Model.Biomolecules · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Cell-to-cell transmission of misfolding-prone α-synuclein (α-Syn) has emerged as a key pathological event in Parkinson's disease. This process is initiated when α-Syn-bearing fibrils enter cells via clathrin-mediated endocytosis, but the underlying mechanisms are unclear. Using a CRISPR-mediated knockout screen, we identify SLC35B2 and myosin-7B (MYO7B) as critical endocytosis regulators for α-Syn preformed fibrils (PFFs). We show that SLC35B2, as a key regulator of heparan sulfate proteoglycan (HSPG) biosynthesis, is essential for recruiting α-Syn PFFs to the cell surface because this process is mediated by interactions between negatively charged sugar moieties of HSPGs and clustered K-T-K motifs in α-Syn PFFs. By contrast, MYO7B regulates α-Syn PFF cell entry by maintaining a plasma membrane-associated actin network that controls membrane dynamics. Without MYO7B or actin filaments, many clathrin-coated pits fail to be severed from the membrane, causing accumulation of large clathrin-containing "scars" on the cell surface. Intriguingly, the requirement for MYO7B in endocytosis is restricted to α-Syn PFFs and other polycation-bearing cargos that enter cells via HSPGs. Thus, our study not only defines regulatory factors for α-Syn PFF endocytosis, but also reveals a previously unknown endocytosis mechanism for HSPG-binding cargos in general, which requires forces generated by MYO7B and actin filaments.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.