ArticleThe EMBO journal2024
GOLPH3 and GOLPH3L maintain Golgi localization of LYSET and a functional mannose 6-phosphate transport pathway.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Molecular regulation and physiological role of GOLPH3-mediated Golgi retention.Nature communications · 2026Article
- GRASP55 maintains lysosome function by controlling sorting of lysosomal enzymes at the Golgi.EMBO reports · 2026Article
- Molecular insights into the regulation of GNPTαβ by LYSET.Nature communications · 2026Article
- A class of COPI cargo receptors regulates processing of transmembrane proteins by reinforcing their Golgi retention.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Ythdc1-p300-Klf5 Complex-Mediated Golgi Dysfunction Promotes Aortic Aneurysm.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Proteomics Insights Into Lysosome Biogenesis and Maturation.Proteomics · 2025Review
- Identification of the client-binding site on the Golgi membrane protein adaptor Vps74/yGOLPH3.iScience · 2025Article
- The mechanistic basis of cargo selection during Golgi maturation.Science advances · 2025Article
- The highly expressedJournal of gastrointestinal oncology · 2025Article
- Luteolin modulates liver macrophage subtype polarization and play protective role in sepsis induced acute hepatic injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
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Authors and funding
19 authors.
Funding
Abstract
Glycosylation, which plays an important role in modifying lipids and sorting of proteins, is regulated by asymmetric intra-Golgi distribution and SPPL3-mediated cleavage of Golgi enzymes. We found that cells lacking LYSET/TMEM251, a retention factor for Golgi N-acetylglucosamine-1-phosphotransferase (GNPT), display SPPL3-dependent hypersecretion of the Golgi membrane protein B4GALT5. We demonstrate that in wild-type cells B4GALT5 is tagged with mannose 6-phosphate (M6P), a sorting tag typical of soluble lysosomal hydrolases. Hence, M6P-tagging of B4GALT5 may represent a novel degradative lysosomal pathway. We also observed B4GALT5 hypersecretion and prominent destabilization of LYSET-GNPT complexes, impaired M6P-tagging, and disturbed maturation and trafficking of lysosomal enzymes in multiple human cell lines lacking the COPI adaptors GOLPH3 and GOLPH3L. Mechanistically, we identified LYSET as a novel, atypical client of GOLPH3/GOLPH3L. Thus, by ensuring the cis-Golgi localization of the LYSET-GNPT complex and maintaining its Golgi polarity, GOLPH3/GOLPH3L is essential for the integrity of the M6P-tagging machinery and homeostasis of lysosomes.
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