ARL15 modulates magnesium homeostasis through N-glycosylation of CNNMs
| العنوان: | ARL15 modulates magnesium homeostasis through N-glycosylation of CNNMs |
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| المؤلفون: | Luis Alfonso Martínez-Cruz, Femke Latta, Serge Hardy, Jonathan Boulais, Joost G. J. Hoenderop, Gijs A C Franken, Jean-François Côté, Chao Ma, Antonio Díaz Quintana, Yevgen Zolotarov, Michel L. Tremblay, Marie-Pier Thibault, Jeroen H. F. de Baaij, Elie Kostantin, Noriko Uetani, Irene González-Recio, Irene Díaz-Moreno |
| المساهمون: | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular, Junta de Andalucía, Ministerio de Ciencia e Innovación (MICIN). España |
| المصدر: | idUS. Depósito de Investigación de la Universidad de Sevilla instname Cellular and Molecular Life Sciences, 78, 13, pp. 5427-5445 Cellular and Molecular Life Sciences, 78, 5427-5445 Cellular and Molecular Life Sciences |
| بيانات النشر: | Cold Spring Harbor Laboratory, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Models, Molecular, 0301 basic medicine, Glycosylation, In silico, GTPase, Protein–protein interaction, Cellular and Molecular Neuroscience, symbols.namesake, chemistry.chemical_compound, 03 medical and health sciences, Protein-protein interaction, 0302 clinical medicine, N-linked glycosylation, Cyclins, Homeostasis, Humans, Magnesium, Small GTPase, Molecular Biology, CNNM2, 030304 developmental biology, Cyclin, Pharmacology, 0303 health sciences, Gene knockdown, CNNM3, ADP-Ribosylation Factors, Chemistry, Endoplasmic reticulum, Magnesium transport, Biological Transport, Cell Biology, Golgi apparatus, Subcellular localization, Cell biology, HEK293 Cells, 030104 developmental biology, Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Cell culture, symbols, Molecular Medicine, Original Article, 030217 neurology & neurosurgery, Protein Binding |
| الوصف: | Cyclin M (CNNM1-4) proteins maintain cellular and body magnesium (Mg2+) homeostasis. Using various biochemical approaches, we have identified members of the CNNM family as direct interacting partners of ADP-ribosylation factor-like GTPase 15 (ARL15), a small GTP-binding protein. ARL15 interacts with CNNMs at their carboxyl-terminal conserved cystathionine-β-synthase (CBS) domains. In silico modeling of the interaction between CNNM2 and ARL15 supports that the small GTPase specifically binds the CBS1 and CNBH domains. Immunocytochemical experiments demonstrate that CNNM2 and ARL15 co-localize in the kidney, with both proteins showing subcellular localization in the endoplasmic reticulum, Golgi apparatus and the plasma membrane. Most importantly, we found that ARL15 is required for forming complex N-glycosylation of CNNMs. Overexpression of ARL15 promotes complex N-glycosylation of CNNM3. Mg2+ uptake experiments with a stable isotope demonstrate that there is a significant increase of 25Mg2+ uptake upon knockdown of ARL15 in multiple kidney cancer cell lines. Altogether, our results establish ARL15 as a novel negative regulator of Mg2+ transport by promoting the complex N-glycosylation of CNNMs. European Joint Program for Rare Diseases (EJPRD2019-40) Spanish Ministry of Science and Innovation and Universities (PGC2018-096049-B-I00) Junta de Andalucía (BIO-198, US-1254317 and US-1257019) |
| وصف الملف: | application/pdf |
| تدمد: | 1420-682X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc43bc3701cb4f71ed4f97287b86cbaa https://doi.org/10.1101/2020.09.09.289835 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....fc43bc3701cb4f71ed4f97287b86cbaa |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 1420682X |
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