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: | Alleene V. Strickland, Michela D’Aloia, Michael A. Gonzalez, Jia Huang, Mark T. Rogers, James W. Connell, Ludger Schöls, Stephan Züchner, Hiroyuki Ishiura, Gladys Montenegro, Lisa Baumbach-Reardon, Shoji Tsuji, Jeffery M. Vance, Justin Price, Tine Deconinck, Margaret A. Pericak-Vance, Carla Babalini, Pasqua Montieri, Rachel Allison, Giorgio Bernardi, Rebecca Schüle, Adriana P. Rebelo, Antonio Orlacchio, Evan Reid, Peter De Jonghe |
| المصدر: | The journal of clinical investigation The Journal of clinical investigation 122 (2012): 538–544. doi:10.1172/JCI60560 info:cnr-pdr/source/autori:Montenegro G.; Rebelo A.P., Connell J.; Allison R.; Babalini C.; D'Aloia M.; Montieri P.; Schüle R.; Ishiura H.; Price J.; Strickland A.; Gonzalez M.A.; Baumbach-Reardon L.; Deconinck T.; Huang J.; Bernardi G.; Vance J.M.; Rogers M.T.; Tsuji S.; De Jonghe P.; Pericak-Vance M.A.; Schöls L.; Orlacchio A.; Reid E.; Züchner S./titolo:Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12/doi:10.1172%2FJCI60560/rivista:The Journal of clinical investigation/anno:2012/pagina_da:538/pagina_a:544/intervallo_pagine:538–544/volume:122 The journal of clinical investigation 122(2), 538-544 (2012). doi:10.1172/JCI60560 |
| بيانات النشر: | American Society for Clinical Investigation, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | pathology [Spastic Paraplegia, Hereditary], Spastin, Settore MED/09 - Medicina Interna, DNA Mutational Analysis, Muscle Proteins, genetics [Muscle Proteins], Endoplasmic Reticulum, medicine.disease_cause, metabolism [Endoplasmic Reticulum], Spastic Paraplegia, genetics [Nerve Tissue Proteins], Exome sequencing, Adenosine Triphosphatases, Genetics, Mutation, Medicine (all), General Medicine, genetics [Adenosine Triphosphatases], genetics [Membrane Proteins], Hereditary, Research Article, Hereditary spastic paraplegia, ultrastructure [Endoplasmic Reticulum], metabolism [Muscle Proteins], Nerve Tissue Proteins, Biology, HeLa Cells, Humans, HEK293 Cells, Spastic Paraplegia, Hereditary, Membrane Proteins, Frameshift mutation, genetics [Spastic Paraplegia, Hereditary], physiopathology [Spastic Paraplegia, Hereditary], RTN2 protein, human, SPAST protein, human, medicine, ddc:610, Gene, metabolism [Nerve Tissue Proteins], medicine.disease, Membrane protein, Reticulon, Human medicine, metabolism [Adenosine Triphosphatases], metabolism [Membrane Proteins] |
| 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. |
| وصف الملف: | |
| تدمد: | 0021-9738 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::79adc26c3da7a07c507da53f4135f3afTest https://doi.org/10.1172/jci60560Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....79adc26c3da7a07c507da53f4135f3af |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00219738 |
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