ArticleNature communications2023
Cell surface protein aggregation triggers endocytosis to maintain plasma membrane proteostasis.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Priming Cells with Modulators of Cellular Signaling Ensures Enhanced Selectivity of HSPG-Specific Protein-Drug Conjugate Delivery.Journal of the American Chemical Society · 2026Article
- Functional Specialization of Clathrin-Independent Endocytic Routes: Mechanisms and Cellular Roles.Traffic (Copenhagen, Denmark) · 2026Review
- Multiparatopic antibodies overcome tyrosine kinase inhibitor resistance by inducing lysosomal degradation of EGFR mutants.Oncogene · 2026Article
- Studying Macromolecular Composition in Cell-Cell Interfaces Using 3D Membrane Reconstitution Systems.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PROTAC internalization and target degradation require clathrin-mediated endocytosis.bioRxiv : the preprint server for biology · 2026Article
- Antibody-induced internalization and degradation of PLA2R amplifies CD4Theranostics · 2026Article
- SARS-CoV-2 pseudoparticles preferentially infect ectoderm in human embryonic tissues.Frontiers in cell and developmental biology · 2026Article
- In-feedFrontiers in physiology · 2026Article
- Enhancing Anti-Tumor Effects of Engineered Extracellular Vesicles via Endocytosis Route Switching and Interferon Response Suppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Monitoring Endocytosis of Integral Membrane Proteins Using Western Blot-Based Detection of Biotinylated Antibody Uptake.Bio-protocol · 2025Article
- Environmental protein corona on nanoplastics altered the responses of skin keratinocytes and fibroblast cells to the particles.Journal of hazardous materials · 2025Article
- Innately Fluorescent Tetravalent Cytotoxic Conjugate TetraFJournal of medicinal chemistry · 2025Article
- Reprogramming FGF1 from the natural growth factor to the engineered heparan sulphate biosensor.Cell communication and signaling : CCS · 2025Article
- Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins.Science (New York, N.Y.) · 2025Article
- Opportunities and Challenges in Antibody-Drug Conjugates for Cancer Therapy: A New Era for Cancer Treatment.Cancers · 2025Review
- In vivo human T cell engineering with enveloped delivery vehicles.Nature biotechnology · 2024Article
- Antidepressant-induced membrane trafficking regulates blood-brain barrier permeability.Molecular psychiatry · 2024Article
- Engineered Antibodies as Cancer Radiotheranostics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Modulations of the mTORC2-GATA3 axis by an isorhamnetin activated endosomal-lysosomal system of the J774.1 macrophage-like cell line.Journal of clinical biochemistry and nutrition · 2024Article
- A Generic Approach for Miniaturized Unbiased High-Throughput Screens of Bispecific Antibodies and Biparatopic Antibody-Drug Conjugates.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The ability of cells to manage consequences of exogenous proteotoxicity is key to cellular homeostasis. While a plethora of well-characterised machinery aids intracellular proteostasis, mechanisms involved in the response to denaturation of extracellular proteins remain elusive. Here we show that aggregation of protein ectodomains triggers their endocytosis via a macroendocytic route, and subsequent lysosomal degradation. Using ERBB2/HER2-specific antibodies we reveal that their cross-linking ability triggers specific and fast endocytosis of the receptor, independent of clathrin and dynamin. Upon aggregation, canonical clathrin-dependent cargoes are redirected into the aggregation-dependent endocytosis (ADE) pathway. ADE is an actin-driven process, which morphologically resembles macropinocytosis. Physical and chemical stress-induced aggregation of surface proteins also triggers ADE, facilitating their degradation in the lysosome. This study pinpoints aggregation of extracellular domains as a trigger for rapid uptake and lysosomal clearance which besides its proteostatic function has potential implications for the uptake of pathological protein aggregates and antibody-based therapies.
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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.