ArticleThe Journal of clinical investigation2010
Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 235 papers, 1 of them a synthesis that pooled it.
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Who cites it
235 citing papers in PubMed, 1 synthesis or guideline pooled it, 381 citations in OpenAlex.
- Genome-wide interaction study with major depression identifies novel variants associated with cognitive function.Molecular psychiatry · 2022Pooled 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
- Mammalian MemPrep establishes the lipid composition of ER membranes in HEK293T cells.EMBO reports · 2026Article
- Proteomic analysis reveals early pathological defects in corticospinal motor neurons of a spastin model of hereditary spastic paraplegia, which are improved by NU-9 treatment.Neurobiology of disease · 2026Article
- Endovascular stem cell therapy reconfigures post-stroke ER dynamics via GRP78/Atlastin/CHOP axis.Molecular brain · 2026Article
- Membrane Protein Folding and Biogenesis: Insights from Single-Molecule Force Spectroscopy.Chemical reviews · 2026Review
- Genotype-structure-phenotype correlations define divergent natural history in early-onset spastic paraplegia type 4.Brain : a journal of neurology · 2026Article
- Modeling spastic paraplegia 4 with corticospinal motor neuron-enriched cortical organoids reveals genotype-phenotype and HDAC6-targetable pathology.Cell reports · 2026Article
- REEP1 Accumulation Disrupts ER Integrity and Drives Spinal Motoneuron Degeneration in Distal Hereditary Motor Neuropathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Serum fucosylated receptor expression-enhancing protein 5 as a biomarker for early stage pancreatic cancer.Oncology letters · 2025Article
- The neuropathy-linked protein TECPR2 is a Rab5 effector that regulates cargo recycling from early endosomes.Nature communications · 2025Article
- LXR agonist rescues synaptic dysfunction and degeneration in SPG3A patient-specific iPSC-derived neurons.Acta neuropathologica communications · 2025Article
- Loss of mouse C19orf12 homolog disturbs tubular ER homeostasis and leads to neuroaxonal dystrophy.Acta neuropathologica communications · 2025Article
- 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
- Wings of Discovery: UsingCells · 2025Review
- Article
- Connecting tubules: mechanisms of endoplasmic reticulum membrane fusion.Biochemical Society transactions · 2025Review
- Lipid droplet accumulation in microglia and their potential roles.Lipids in health and disease · 2025Review
- PERK-dependent reciprocal crosstalk between ER and non-centrosomal microtubules coordinates ER architecture and cell shape.Cell reports · 2025Article
175 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Hereditary spastic paraplegias (HSPs; SPG1-45) are inherited neurological disorders characterized by lower extremity spastic weakness. More than half of HSP cases result from autosomal dominant mutations in atlastin-1 (also known as SPG3A), receptor expression enhancing protein 1 (REEP1; SPG31), or spastin (SPG4). The atlastin-1 GTPase interacts with spastin, a microtubule-severing ATPase, as well as with the DP1/Yop1p and reticulon families of ER-shaping proteins, and SPG3A caused by atlastin-1 mutations has been linked pathogenically to abnormal ER morphology. Here we investigated SPG31 by analyzing the distribution, interactions, and functions of REEP1. We determined that REEP1 is structurally related to the DP1/Yop1p family of ER-shaping proteins and localizes to the ER in cultured rat cerebral cortical neurons, where it colocalizes with spastin and atlastin-1. Upon overexpression in COS7 cells, REEP1 formed protein complexes with atlastin-1 and spastin within the tubular ER, and these interactions required hydrophobic hairpin domains in each of these proteins. REEP proteins were required for ER network formation in vitro, and REEP1 also bound microtubules and promoted ER alignment along the microtubule cytoskeleton in COS7 cells. A SPG31 mutant REEP1 lacking the C-terminal cytoplasmic region did not interact with microtubules and disrupted the ER network. These data indicate that the HSP proteins atlastin-1, spastin, and REEP1 interact within the tubularER membrane in corticospinal neurons to coordinate ER shaping and microtubule dynamics. Thus, defects in tubular ER shaping and network interactions with the microtubule cytoskeleton seem to be the predominant pathogenic mechanism of 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.