A y+LAT-1 mutant protein interferes with y+LAT-2 activity: implications for the molecular pathogenesis of lysinuric protein intolerance
| العنوان: | A y+LAT-1 mutant protein interferes with y+LAT-2 activity: implications for the molecular pathogenesis of lysinuric protein intolerance |
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| المؤلفون: | Chiara Zurzolo, Maria Pia Sperandeo, Simona Paladino, Luigi Maiuri, Gianfranco Sebastio, George D Maroupulos, Maurizio Taglialatela, Generoso Andria |
| المساهمون: | Department of Pediatrics, Università degli studi di Napoli Federico II, Dulbecco Telethon Institute, Telethon Foundation, Dipartimento di Biologia e Patologia Cellulare e Moleculare, Biochemistry Laboratory, General Children's Hospital of Athens P & A Kyriakou, Trafic membranaire et Pathogénèse, Institut Pasteur [Paris], Section of Pharmacology, Sperandeo, Mp, Paladino, S, Maiuri, L, Maroupulos, Gd, Zurzolo, Chiara, Taglialatela, M, Andria, Generoso, Sebastio, Gianfranco, Sperandeo, M. P., Paladino, Simona, Maiuri, L., Maroupulos, G. D., Taglialatela, Maurizio, Andria, G., Sebastio, G., University of Naples Federico II = Università degli studi di Napoli Federico II, Institut Pasteur [Paris] (IP) |
| المصدر: | European Journal of Human Genetics European Journal of Human Genetics, Nature Publishing Group, 2005, 13 (5), pp.628-34. ⟨10.1038/sj.ejhg.5201376⟩ European Journal of Human Genetics, 2005, 13 (5), pp.628-34. ⟨10.1038/sj.ejhg.5201376⟩ |
| بيانات النشر: | Springer Science and Business Media LLC, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Male, Mutant, Xenopus, medicine.disease_cause, MESH: Dogs, Xenopus laevis, 0302 clinical medicine, prottein trafficking, Mutant protein, MESH: Animals, skin and connective tissue diseases, Genetics (clinical), Epithelial polarity, 0303 health sciences, Mutation, amino acid transport, biology, Fusion Regulatory Protein 1, Light Chains, MESH: Arginine, Amino Acid Transport System y+L, Biochemistry, Child, Preschool, MESH: Amino Acid Transport Systems, Basic, MESH: Mutation, Protein subunit, Arginine, Cell Line, MESH: Oocytes, 03 medical and health sciences, Dogs, MESH: Xenopus laevis, Genetics, medicine, Animals, Humans, MESH: Amino Acid Metabolism, Inborn Errors, MESH: Lysine, Amino Acid Metabolism, Inborn Errors, 030304 developmental biology, MESH: Humans, Lysine, MESH: Child, Preschool, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, medicine.disease, Lysinuric protein intolerance, Molecular biology, MESH: Male, MESH: Cell Line, SLC7A7 Gene, yþLAT-1/-2, lysinuric protein intolerance, Oocytes, Amino Acid Transport Systems, Basic, MESH: Antigens, CD98 Light Chains, 030217 neurology & neurosurgery |
| الوصف: | Lysinuric protein intolerance (LPI) is an inherited aminoaciduria caused by defective cationic amino acid (CAA) transport at the basolateral membrane of epithelial cells in the intestine and kidney. The SLC7A7 gene, mutated in LPI, encodes the y(+)LAT-1 protein, which is the light subunit of the heterodimeric CAA transporter in which 4F2hc is the heavy chain subunit. Co-expression of 4F2hc and y(+)LAT-1 induces the y(+)L activity. This activity is also exerted by another complex composed of 4F2hc and y(+)LAT-2, the latter encoded by the SLC7A6 gene and more ubiquitously expressed than SLC7A7. On the basis of both the pattern of expression and the transport activity, y(+)LAT-2 might compensate for CAA transport when y(+)LAT-1 is defective. By expression in Xenopus laevis oocytes and mammalian cells, we functionally analysed two SLC7A7 mutants, E36del and F152L, respectively, the former displaying a partial dominant-negative effect. The results of the present study provide further insight into the molecular pathogenesis of LPI: a putative multiheteromeric structure of both [4F2hc/y(+)LAT-1] and [4F2hc/y(+)LAT-2], and the interference between y(+)LAT-1 and y(+)LAT-2 proteins. This interference can explain why the compensatory mechanism, that is, an increased expression of SLC7A6 as seen in lymphoblasts from LPI patients, may not be sufficient to restore the y(+)L system activity. |
| وصف الملف: | STAMPA |
| تدمد: | 1476-5438 1018-4813 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::141cd387c7c1d38ed19cc8d095cd2b2fTest https://doi.org/10.1038/sj.ejhg.5201376Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....141cd387c7c1d38ed19cc8d095cd2b2f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765438 10184813 |
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