ArticleThe Journal of cell biology2024
Alternative mechanisms of Notch activation by partitioning into distinct endosomal domains.
Article in The Journal of cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Analysis of cancer mutations introduced into theeLife · 2026Article
- The Notch1 intracellular domain orchestrates mechanotransduction of fluid shear stress.Life science alliance · 2026Article
- Neuropeptide Y YNaunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Extracellular domain shedding of NOTCH3 during endocytosis associated with heterogeneity between different CADASIL mutant activation mechanisms.Cell communication and signaling : CCS · 2025Article
- The Memory Gene,Biomolecules · 2025Article
- Modes of Notch signalling in development and disease.Nature reviews. Molecular cell biology · 2025Review
- Autophagy controls differentiation of Drosophila blood cells by regulating Notch levels in response to nutrient availability.Nature communications · 2025Article
- The Abelson kinase and the Nedd4 family E3 ligases co-regulate Notch trafficking to limit signaling.The Journal of cell biology · 2025Article
- Synergistic Crosstalk of PACAP and Notch Signaling Pathways in Bone Development.International journal of molecular sciences · 2025Article
- Hemifusomes and interacting proteolipid nanodroplets mediate multi-vesicular body formation.Nature communications · 2025Article
- Endosomal membrane budding patterns in plants.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Hemifusomes and Interacting Proteolipid Nanodroplets Mediate Multi-Vesicular Body Formation.Research square · 2024Article
- Article
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
Different membrane microdomain compositions provide unique environments that can regulate signaling receptor function. We identify microdomains on the endosome membrane of Drosophila endosomes, enriched in lipid-raft or clathrin/ESCRT-0, which are associated with Notch activation by distinct, ligand-independent mechanisms. Transfer of Notch between microdomains is regulated by Deltex and Suppressor of deltex ubiquitin ligases and is limited by a gate-keeper role for ESCRT complexes. Ubiquitination of Notch by Deltex recruits it to the clathrin/ESCRT-0 microdomain and enhances Notch activation by an ADAM10-independent/TRPML-dependent mechanism. This requirement for Deltex is bypassed by the downregulation of ESCRT-III. In contrast, while ESCRT-I depletion also activates Notch, it does so by an ADAM10-dependent/TRPML-independent mechanism and Notch is retained in the lipid raft-like microdomain. In the absence of such endosomal perturbation, different activating Notch mutations also localize to different microdomains and are activated by different mechanisms. Our findings demonstrate the interplay between Notch regulators, endosomal trafficking components, and Notch genetics, which defines membrane locations and activation mechanisms.
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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 Socratic graph.