ArticleMolecular and cellular biology2012
Mannose 6 dephosphorylation of lysosomal proteins mediated by acid phosphatases Acp2 and Acp5.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 55 citations in OpenAlex.
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- Disruption of Man-6-P-Dependent Sorting to Lysosomes Confers IGF1R-Mediated Apoptosis Resistance.International journal of molecular sciences · 2025Article
- Spatial Organization of the Sperm Cell Glycoproteome.Molecular & cellular proteomics : MCP · 2025Article
- Production of Domain 9 from the cation-independent mannose-6-phosphate receptor fused with an Fc domain.Glycoconjugate journal · 2024Article
- High throughput screen identifies lysosomal acid phosphatase 2 (ACP2) to regulate IFN-1 responses to potentiate oncolytic VSV∆51 activity.Scientific reports · 2024Article
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- Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4.Structure (London, England : 1993) · 2024Article
- Nε-Carboxymethyl-Lysine Mediates Vascular Calcification in Diabetes Caused by Impaired Osteoclastic Resorption Activity Through NFATc1-GNPTAB.Journal of cardiovascular translational research · 2023Article
- Comparative site-specific N-glycoproteome analysis reveals aberrant N-glycosylation and gives insights into mannose-6-phosphate pathway in cancer.Communications biology · 2023Article
- Enamel defects in Acp4Scientific reports · 2022Article
- AMPylation profiling during neuronal differentiation reveals extensive variation on lysosomal proteins.iScience · 2021Article
- Dual-Functional Ti(IV)-IMAC Material Enables Simultaneous Enrichment and Separation of Diverse Glycopeptides and Phosphopeptides.Analytical chemistry · 2021Article
- Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis and Phenotyping of Carotid Artery Stenosis.Frontiers in molecular biosciences · 2021Article
- Alteration of the Dopamine Receptors' Expression in the Cerebellum of the Lysosomal Acid Phosphatase 2 Mutant (Naked-Ataxia (International journal of molecular sciences · 2020Article
- Comprehensive draft of the mouse embryonic fibroblast lysosomal proteome by mass spectrometry based proteomics.Scientific data · 2020Article
- Infant Alveolar Macrophages Are Unable to Effectively ContainFrontiers in immunology · 2020Article
- Mannose 6-phosphonate labelling: A key for processing the therapeutic enzyme in Pompe disease.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mannose 6-phosphate (Man6P) residues represent a recognition signal required for efficient receptor-dependent transport of soluble lysosomal proteins to lysosomes. Upon arrival, the proteins are rapidly dephosphorylated. We used mice deficient for the lysosomal acid phosphatase Acp2 or Acp5 or lacking both phosphatases (Acp2/Acp5(-/-)) to examine their role in dephosphorylation of Man6P-containing proteins. Two-dimensional (2D) Man6P immunoblot analyses of tyloxapol-purified lysosomal fractions revealed an important role of Acp5 acting in concert with Acp2 for complete dephosphorylation of lysosomal proteins. The most abundant lysosomal substrates of Acp2 and Acp5 were identified by Man6P affinity chromatography and mass spectrometry. Depending on the presence of Acp2 or Acp5, the isoelectric point of the lysosomal cholesterol-binding protein Npc2 ranged between 7.0 and 5.4 and may thus regulate its interaction with negatively charged lysosomal membranes at acidic pH. Correspondingly, unesterified cholesterol was found to accumulate in lysosomes of cultured hepatocytes of Acp2/Acp5(-/-) mice. The data demonstrate that dephosphorylation of Man6P-containing lysosomal proteins requires the concerted action of Acp2 and Acp5 and is needed for hydrolysis and removal of degradation products.
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