ArticleMolecular biology of the cell2013
Mutation of SIMPLE in Charcot-Marie-Tooth 1C alters production of exosomes.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
64 citing papers in PubMed, 94 citations in OpenAlex.
- Molecular Mechanisms of Extracellular Vesicle Biogenesis and Their Impact on the Design of Custom EVs.Advanced healthcare materials · 2025Review
- Extracellular Vesicles and Immune Activation in Solid Organ Transplantation: The Impact of Immunosuppression.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Current trends in theranostic applications of extracellular vesicles in cancer.Frontiers in oncology · 2025Review
- The biology of exosomes and exosomal non-coding RNAs in cardiovascular diseases.Frontiers in pharmacology · 2025Review
- A Role of Inflammation in Charcot-Marie-Tooth Disorders-In a Perspective of Treatment?International journal of molecular sciences · 2024Review
- miRNA packaging into small extracellular vesicles and implications in pain.Pain reports · 2024Review
- Emerging Roles of Small Extracellular Vesicles in Gastrointestinal Cancer Research and Therapy.Cancers · 2024Review
- LITAF protects against pore-forming protein-induced cell death by promoting membrane repair.Science immunology · 2024Article
- Schwann cells in the normal and pathological lung microenvironment.Frontiers in molecular biosciences · 2024Review
- Exosome-Autophagy Crosstalk in Enveloped Virus Infection.International journal of molecular sciences · 2023Review
- Review
- The Machinery of Exosomes: Biogenesis, Release, and Uptake.International journal of molecular sciences · 2023Review
- Contribution of Extracellular Vesicles and Molecular Chaperones in Age-Related Neurodegenerative Disorders of the CNS.International journal of molecular sciences · 2023Review
- Neuron-Schwann cell interactions in peripheral nervous system homeostasis, disease, and preclinical treatment.Frontiers in cellular neuroscience · 2023Review
- Extracellular vesicles, from the pathogenesis to the therapy of neurodegenerative diseases.Translational neurodegeneration · 2022Review
- The Influence of Proteins on Fate and Biological Role of Circulating DNA.International journal of molecular sciences · 2022Review
- The Role of Extracellular Vesicles in Cancer-Nerve Crosstalk of the Peripheral Nervous System.Cells · 2022Review
- Vesicular Ganglioside GM1 From Breast Tumor Cells Stimulated Epithelial-to-Mesenchymal Transition of Recipient MCF-10A Cells.Frontiers in oncology · 2022Article
- Review
- MSCs and their exosomes: a rapidly evolving approach in the context of cutaneous wounds therapy.Stem cell research & therapy · 2021Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Charcot-Marie-Tooth (CMT) disease is an inherited neurological disorder. Mutations in the small integral membrane protein of the lysosome/late endosome (SIMPLE) account for the rare autosomal-dominant demyelination in CMT1C patients. Understanding the molecular basis of CMT1C pathogenesis is impeded, in part, by perplexity about the role of SIMPLE, which is expressed in multiple cell types. Here we show that SIMPLE resides within the intraluminal vesicles of multivesicular bodies (MVBs) and inside exosomes, which are nanovesicles secreted extracellularly. Targeting of SIMPLE to exosomes is modulated by positive and negative regulatory motifs. We also find that expression of SIMPLE increases the number of exosomes and secretion of exosome proteins. We engineer a point mutation on the SIMPLE allele and generate a physiological mouse model that expresses CMT1C-mutated SIMPLE at the endogenous level. We find that CMT1C mouse primary embryonic fibroblasts show decreased number of exosomes and reduced secretion of exosome proteins, in part due to improper formation of MVBs. CMT1C patient B cells and CMT1C mouse primary Schwann cells show similar defects. Together the data indicate that SIMPLE regulates the production of exosomes by modulating the formation of MVBs. Dysregulated endosomal trafficking and changes in the landscape of exosome-mediated intercellular communications may place an overwhelming burden on the nervous system and account for CMT1C molecular pathogenesis.
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Registered trials
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.