ArticleProceedings of the National Academy of Sciences of the United States of America2022
Selective inhibition of protein secretion by abrogating receptor-coat interactions during ER export.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Site-specific glycosylation of Sec24D and myoferlin recruit ERGIC to ER exit sites for collagen trafficking.Nature communications · 2026Article
- Article
- Towards a unified framework for the function of endoplasmic reticulum exit sites.Nature reviews. Molecular cell biology · 2025Review
- Mechanisms of COPII coat assembly and cargo recognition in the secretory pathway.Nature reviews. Molecular cell biology · 2025Review
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- A Novel Small-Molecule GRP94 Modulator Increases PCSK9 Secretion and Promotes LDLR Degradation.Life (Basel, Switzerland) · 2025Article
- A light-resuming strategy as a screening method for selecting Sec61 inhibitors down-modulating PD-L1 expression.Nature communications · 2025Article
- ER export via SURF4 uses diverse mechanisms of both client and coat engagement.The Journal of cell biology · 2025Article
- Genetics of hemostasis: from bedside to bench and back again.The Journal of clinical investigation · 2024Article
- Protein condensates in the the secretory pathway: Unraveling biophysical interactions and function.Biophysical journal · 2024Review
- TANGO1 inhibitors reduce collagen secretion and limit tissue scarring.Nature communications · 2024Article
- ER exit in physiology and disease.Frontiers in molecular biosciences · 2024Review
- Nlp-dependent ER-to-Golgi transport.International journal of biological sciences · 2024Article
- Steady-state regulation of COPII-dependent secretory cargo sorting by inositol trisphosphate receptors, calcium, and penta EF hand proteins.The Journal of biological chemistry · 2023Article
- Identification of LMAN1- and SURF4-Dependent Secretory Cargoes.Journal of proteome research · 2023Article
- Mammalian cargo receptors for endoplasmic reticulum-to-Golgi transport: mechanisms and interactions.Biochemical Society transactions · 2023Review
- Quantification of the Chemical Chaperone 4-Phenylbutyric Acid (4-PBA) in Cell Culture Media via LC-HRMS: Applications in Fields of Neurodegeneration and Cancer.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Cargo selection in endoplasmic reticulum-to-Golgi transport and relevant diseases.The Journal of clinical investigation · 2023Review
- Hepatic inactivation of murineeLife · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Protein secretion is an essential process that drives cell growth, movement, and communication. Protein traffic within the secretory pathway occurs via transport intermediates that bud from one compartment and fuse with a downstream compartment to deliver their contents. Here, we explore the possibility that protein secretion can be selectively inhibited by perturbing protein-protein interactions that drive capture into transport vesicles. Human proprotein convertase subtilisin/kexin type 9 (PCSK9) is a determinant of cholesterol metabolism whose secretion is mediated by a specific cargo adaptor protein, SEC24A. We map a series of protein-protein interactions between PCSK9, its endoplasmic reticulum (ER) export receptor SURF4, and SEC24A that mediate secretion of PCSK9. We show that the interaction between SURF4 and SEC24A can be inhibited by 4-phenylbutyrate (4-PBA), a small molecule that occludes a cargo-binding domain of SEC24. This inhibition reduces secretion of PCSK9 and additional SURF4 clients that we identify by mass spectrometry, leaving other secreted cargoes unaffected. We propose that selective small-molecule inhibition of cargo recognition by SEC24 is a potential therapeutic intervention for atherosclerosis and other diseases that are modulated by secreted proteins.
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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.