ArticleNature communications2022
GCAF(TMEM251) regulates lysosome biogenesis by activating the mannose-6-phosphate pathway.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 38 citations in OpenAlex.
- GRASP55 maintains lysosome function by controlling sorting of lysosomal enzymes at the Golgi.EMBO reports · 2026Article
- Peroxisome-derived ether lipids regulate lysosomal exocytosis.The EMBO journal · 2026Article
- Molecular insights into the regulation of GNPTαβ by LYSET.Nature communications · 2026Article
- Unraveling Lysosomal Exocytosis: From Molecular Mechanisms to Physiological Functions.Traffic (Copenhagen, Denmark) · 2026Review
- TMEM251 loss-induced autophagy dysfunction in the anterior cingulate cortex contributes to chronic postoperative pain.EMBO reports · 2026Article
- Lysosomal membrane homeostasis and its importance in physiology and disease.Nature reviews. Molecular cell biology · 2026Review
- Proteomics Insights Into Lysosome Biogenesis and Maturation.Proteomics · 2025Review
- ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver.Communications biology · 2025Article
- Syntaxin-2 balances phagocytic uptake and phagolysosomal clearance in macrophages.Journal of cell science · 2025Article
- Coxiella burnetii manipulates the lysosomal protease cathepsin B to facilitate intracellular success.Nature communications · 2025Article
- LYSET facilitates integration of both the N- and C-terminal transmembrane helices/cytoplasmic domains of GlcNAc-1-phosphotransferase.Molecular biology of the cell · 2025Article
- GRASP55 regulates sorting and maturation of the lysosomal enzyme β-hexosaminidase A.Molecular biology of the cell · 2025Article
- Exploring the molecular mechanisms of tirzepatide in alleviating metabolic dysfunction-associated fatty liver in mice through integration of metabolomics, lipidomics, and proteomics.Lipids in health and disease · 2025Article
- Clinical and molecular characteristics of 20 Chinese probands with Mucolipidosis type II and III alpha/beta.BMC pediatrics · 2024Article
- Characterization of Site-Specific N- and O-Glycopeptides from Recombinant Spike and ACE2 Glycoproteins Using LC-MS/MS Analysis.International journal of molecular sciences · 2024Article
- GOLPH3 and GOLPH3L maintain Golgi localization of LYSET and a functional mannose 6-phosphate transport pathway.The EMBO journal · 2024Article
- Production of Domain 9 from the cation-independent mannose-6-phosphate receptor fused with an Fc domain.Glycoconjugate journal · 2024Article
- A genetically-encoded fluorescence-based reporter to spatiotemporally investigate mannose-6-phosphate pathway.Molecular biology of the cell · 2024Article
- Review
- Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology.Nature reviews. Molecular cell biology · 2024Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
The mannose-6-phosphate (M6P) biosynthetic pathway for lysosome biogenesis has been studied for decades and is considered a well-understood topic. However, whether this pathway is regulated remains an open question. In a genome-wide CRISPR/Cas9 knockout screen, we discover TMEM251 as the first regulator of the M6P modification. Deleting TMEM251 causes mistargeting of most lysosomal enzymes due to their loss of M6P modification and accumulation of numerous undigested materials. We further demonstrate that TMEM251 localizes to the Golgi and is required for the cleavage and activity of GNPT, the enzyme that catalyzes M6P modification. In zebrafish, TMEM251 deletion leads to severe developmental defects including heart edema and skeletal dysplasia, which phenocopies Mucolipidosis Type II. Our discovery provides a mechanism for the newly discovered human disease caused by TMEM251 mutations. We name TMEM251 as GNPTAB cleavage and activity factor (GCAF) and its related disease as Mucolipidosis Type V.
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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.