ArticleNature communications2014
Lysosome sorting of β-glucocerebrosidase by LIMP-2 is targeted by the mannose 6-phosphate receptor.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 92 citations in OpenAlex.
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- Enzyme Activity-Based Genome-wide Screening for Modifiers of Lysosomal Glucocerebrosidase Uncovers Candidate Risk Factors for Parkinson's Disease.ACS central science · 2025Article
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- Cryo-TEM structure of β-glucocerebrosidase in complex with its transporter LIMP-2.Nature communications · 2025Article
- A genome-wide atlas of human cell morphology.Nature methods · 2025Article
- Multi-omic analysis of a mucolipidosis II neuronal cell model uncovers involvement of pathways related to neurodegeneration and drug metabolism.Molecular genetics and metabolism · 2024Article
- Activation and Purification of ß-Glucocerebrosidase by Exploiting its Transporter LIMP-2 - Implications for Novel Treatment Strategies in Gaucher's and Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain.Science (New York, N.Y.) · 2024Article
- Article
- Lysosomal membrane proteins LAMP1 and LIMP2 are segregated in the Golgi apparatus independently of their clathrin adaptor binding motif.Molecular biology of the cell · 2024Article
- Enterovirus A71 does not meet the uncoating receptor SCARB2 at the cell surface.PLoS pathogens · 2024Article
- Characterization of Novel Human β-glucocerebrosidase Antibodies for Parkinson's Disease Research.Journal of Parkinson's disease · 2024Article
- Capsid-Specific Antibody Responses of Domestic Pigs Immunized with Low-Virulent African Swine Fever Virus.Vaccines · 2023Article
- A genome-wide atlas of human cell morphology.bioRxiv : the preprint server for biology · 2023Article
- The uncoating of EV71 in mature late endosomes requires CD-M6PR.Biology open · 2022Article
- A versatile fluorescence-quenched substrate for quantitative measurement of glucocerebrosidase activity within live cells.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- SR-B1's Next Top Model: Structural Perspectives on the Functions of the HDL Receptor.Current atherosclerosis reports · 2022Review
- Fc-Mediated Functions of Porcine IgG Subclasses.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The integral membrane protein LIMP-2 has been a paradigm for mannose 6-phosphate receptor (MPR) independent lysosomal targeting, binding to β-glucocerebrosidase (β-GCase) and directing it to the lysosome, before dissociating in the late-endosomal/lysosomal compartments. Here we report structural results illuminating how LIMP-2 binds and releases β-GCase according to changes in pH, via a histidine trigger, and suggesting that LIMP-2 localizes the ceramide portion of the substrate adjacent to the β-GCase catalytic site. Remarkably, we find that LIMP-2 bears P-Man9GlcNAc2 covalently attached to residue N325, and that it binds MPR, via mannose 6-phosphate, with a similar affinity to that observed between LIMP-2 and β-GCase. The binding sites for β-GCase and the MPR are functionally separate, so that a stable ternary complex can be formed. By fluorescence lifetime imaging microscopy, we also demonstrate that LIMP-2 interacts with MPR in living cells. These results revise the accepted view of LIMP-2-β-GCase lysosomal targeting.
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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.