ArticlePLoS biology2021
A conserved ubiquitin- and ESCRT-dependent pathway internalizes human lysosomal membrane proteins for degradation.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 54 citations in OpenAlex.
- Emerging mechanisms of ATG8-independent non-canonical autophagy.Journal of physiology and biochemistry · 2026Review
- Macrophage USP7 aggravates acute myocardial infarction by inhibiting STING degradation through the ESCRT pathway.Cell death and differentiation · 2026Article
- Peroxisome-derived ether lipids regulate lysosomal exocytosis.The EMBO journal · 2026Article
- Molecular engineering of lysosome-based degraders unveils a rapidly expanding therapeutic strategy.Autophagy · 2026Review
- Urine Proteomics as a Source of Biological Information and Outcome Predictor in Living Kidney Transplantation.Molecular & cellular proteomics : MCP · 2026Article
- Molecular insights into the regulation of GNPTαβ by LYSET.Nature communications · 2026Article
- The Roles of SQSTM1/p62 in Selective Autophagy and Oncogenic Signaling.International journal of molecular sciences · 2026Review
- LAPTM proteins in neurological disorders - Autophagy-lysosome dysfunction and therapeutic targets: A review.Biomolecules & biomedicine · 2026Review
- Microautophagy: current understanding of its molecular mechanisms and functions.Autophagy reports · 2026Review
- Laptm4a mediates renal ischemia-reperfusion injury by regulating the UNC5B-AKT/mTOR signaling pathway.Frontiers in immunology · 2026Article
- Article
- Smurf1 promotes gastric cancer progression by regulating Axin2-dependent Wnt signaling pathway.Scientific reports · 2025Article
- CHIP protects lysosomes from CLN4 mutant-induced membrane damage.Nature cell biology · 2025Article
- LYMTACs:chimeric small molecules repurpose lysosomal membrane proteins for target protein relocalization and degradation.Nature communications · 2025Article
- Lysosomal quality control Review.Autophagy · 2025Review
- Review
- Lysosomal Repair in Health and Disease.Journal of cellular physiology · 2025Review
- Protocol for purifying and reconstituting a vacuole membrane transporter Ypq1 into proteoliposomes.STAR protocols · 2024Article
- High frequency electrical stimulation reduces α-synuclein levels and α-synuclein-mediated autophagy dysfunction.Scientific reports · 2024Article
- Lipid-mediated intracellular delivery of recombinant bioPROTACs for the rapid degradation of undruggable proteins.Nature communications · 2024Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The lysosome is an essential organelle to recycle cellular materials and maintain nutrient homeostasis, but the mechanism to down-regulate its membrane proteins is poorly understood. In this study, we performed a cycloheximide (CHX) chase assay to measure the half-lives of approximately 30 human lysosomal membrane proteins (LMPs) and identified RNF152 and LAPTM4A as short-lived membrane proteins. The degradation of both proteins is ubiquitin dependent. RNF152 is a transmembrane E3 ligase that ubiquitinates itself, whereas LAPTM4A uses its carboxyl-terminal PY motifs to recruit NEDD4-1 for ubiquitination. After ubiquitination, they are internalized into the lysosome lumen by the endosomal sorting complexes required for transport (ESCRT) machinery for degradation. Strikingly, when ectopically expressed in budding yeast, human RNF152 is still degraded by the vacuole (yeast lysosome) in an ESCRT-dependent manner. Thus, our study uncovered a conserved mechanism to down-regulate lysosome membrane 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.