دورية أكاديمية
Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12.
| العنوان: | Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12. |
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| المؤلفون: | Montenegro, Gladys, Rebelo, Adriana P, Strickland, Alleene, Gonzalez, Michael A, Baumbach-Reardon, Lisa, Deconinck, Tine, Huang, Jia, Bernardi, Giorgio, Vance, Jeffery M, Rogers, Mark T, Tsuji, Shoji, De Jonghe, Peter, Connell, James, Pericak-Vance, Margaret A, Schöls, Ludger, Orlacchio, Antonio, Reid, Evan, Züchner, Stephan, Allison, Rachel, Babalini, Carla, D'Aloia, Michela, Montieri, Pasqua, Schüle, Rebecca, Ishiura, Hiroyuki, Price, Justin |
| المصدر: | The journal of clinical investigation 122(2), 538-544 (2012). doi:10.1172/JCI60560 |
| بيانات النشر: | ASCJ |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | info:eu-repo/classification/ddc/610, Adenosine Triphosphatases: genetics, Adenosine Triphosphatases: metabolism, DNA Mutational Analysis, Endoplasmic Reticulum: metabolism, Endoplasmic Reticulum: ultrastructure, HEK293 Cells, HeLa Cells, Humans, Membrane Proteins: genetics, Membrane Proteins: metabolism, Muscle Proteins: genetics, Muscle Proteins: metabolism, Mutation, Nerve Tissue Proteins: genetics, Nerve Tissue Proteins: metabolism, Spastic Paraplegia, Hereditary: genetics, Hereditary: pathology, Hereditary: physiopathology, Spastin, Membrane Proteins, Muscle Proteins, Nerve Tissue Proteins, RTN2 protein, human, Adenosine Triphosphatases, SPAST protein |
| جغرافية الموضوع: | DE |
| الوصف: | Hereditary spastic paraplegias (HSPs) are a group of genetically heterogeneous neurodegenerative conditions. They are characterized by progressive spastic paralysis of the legs as a result of selective, length-dependent degeneration of the axons of the corticospinal tract. Mutations in 3 genes encoding proteins that work together to shape the ER into sheets and tubules - receptor accessory protein 1 (REEP1), atlastin-1 (ATL1), and spastin (SPAST) - have been found to underlie many cases of HSP in Northern Europe and North America. Applying Sanger and exome sequencing, we have now identified 3 mutations in reticulon 2 (RTN2), which encodes a member of the reticulon family of prototypic ER-shaping proteins, in families with spastic paraplegia 12 (SPG12). These autosomal dominant mutations included a complete deletion of RTN2 and a frameshift mutation predicted to produce a highly truncated protein. Wild-type reticulon 2, but not the truncated protein potentially encoded by the frameshift allele, localized to the ER. RTN2 interacted with spastin, and this interaction required a hydrophobic region in spastin that is involved in ER localization and that is predicted to form a curvature-inducing/sensing hairpin loop domain. Our results directly implicate a reticulon protein in axonopathy, show that this protein participates in a network of interactions among HSP proteins involved in ER shaping, and further support the hypothesis that abnormal ER morphogenesis is a pathogenic mechanism in HSP. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/issn/0021-9738; info:eu-repo/semantics/altIdentifier/pmid/pmid:22232211; info:eu-repo/semantics/altIdentifier/issn/1558-8238; https://pub.dzne.de/record/136420Test; https://pub.dzne.de/search?p=id:%22DZNE-2020-02742%22Test |
| الإتاحة: | https://doi.org/10.1172/JCI60560Test https://pub.dzne.de/record/136420Test https://pub.dzne.de/search?p=id:%22DZNE-2020-02742%22Test |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.5D34E620 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |