ArticleThe Journal of clinical investigation2012
Mutations in the ER-shaping protein reticulon 2 cause the axon-degenerative disorder hereditary spastic paraplegia type 12.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 1 of them a synthesis that pooled it.
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Who cites it
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 169 citations in OpenAlex.
- Identification of novel genes selectively expressed in the follicle-associated epithelium from the meta-analysis of transcriptomics data from multiple mouse cell and tissue populations.DNA research : an international journal for rapid publication of reports on genes and genomes · 2012Pooled it
- Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Endoplasmic Reticulum Geometry Dictates Neuronal Bursting via Calcium Store Refill Rates and Exposes Selective Neuronal Vulnerability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The diverse forms and roles of the neuronal endoplasmic reticulum.Nature reviews. Neuroscience · 2026Review
- Dynamics of autophagy in response to high linear energy transfer radiation and cancer.Korean journal of clinical oncology · 2025Review
- Tubular ER dysfunction in neurodegenerative diseases.Neurobiology of disease · 2025Review
- Endoplasmic reticulum junctions serve as a platform for endosome-lysosome interactions through their stop-and-go motion switching.Science advances · 2025Article
- Neurodevelopmental Implications Underpinning Hereditary Spastic Paraplegia.CNS neuroscience & therapeutics · 2025Review
- Article
- A novel variant (p.A524P) in Spastin is responsible for a Chinese family with hereditary spastic paraplegia.Molecular biology reports · 2024Article
- Atlastin-1 regulates endosomal tubulation and lysosomal proteolysis in human cortical neurons.Neurobiology of disease · 2024Article
- Fam134c and Fam134b shape axonal endoplasmic reticulum architecture in vivo.EMBO reports · 2024Article
- RTN2 deficiency results in an autosomal recessive distal motor neuropathy with lower limb spasticity.Brain : a journal of neurology · 2024Article
- Increased burden of rare protein-truncating variants in constrained, brain-specific and synaptic genes in extremely impulsively violent males with antisocial personality disorder.Genes, brain, and behavior · 2024Article
- Large-Scale Whole-Genome Analysis of HTLV-1-Associated Myelopathy Identified Hereditary Spastic Paraplegias.Neurology. Genetics · 2024Article
- Proteomic Identification of Seasonally Expressed Proteins Contributing to Heart Function and the Avoidance of Skeletal Muscle Disuse Atrophy in a Hibernating Mammal.Journal of proteome research · 2024Article
- Hereditary spastic paraplegia: Novel insights into the pathogenesis and management.SAGE open medicine · 2024Review
- Article
- Spatacsin regulates directionality of lysosome trafficking by promoting the degradation of its partner AP5Z1.PLoS biology · 2023Article
- Identification of atlastin genetic modifiers in a model of hereditary spastic paraplegia in Drosophila.Human genetics · 2023Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 6 countries.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.