ArticleHuman molecular genetics2010
Mistargeting of SH3TC2 away from the recycling endosome causes Charcot-Marie-Tooth disease type 4C.
Article in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 82 citations in OpenAlex.
- Compound heterozygous mutations of SH3TC2 in Charcot-Marie-Tooth disease type 4C patients.Journal of human genetics · 2019Trial
- Article
- Charcot-Marie-Tooth disease and related neuropathies.Nature reviews. Disease primers · 2026Review
- NT2-derived astrocyte-neuron co-culture reflects physiological relevance and offers research validity.Cellular & molecular biology letters · 2025Article
- Schwann cell deletion ofmicroPublication biology · 2025Article
- A Role of Inflammation in Charcot-Marie-Tooth Disorders-In a Perspective of Treatment?International journal of molecular sciences · 2024Review
- Current Treatment Methods for Charcot-Marie-Tooth Diseases.Biomolecules · 2024Review
- Peripheral Nervous System (PNS) Myelin Diseases.Cold Spring Harbor perspectives in biology · 2024Review
- AAV1.tMCK.NT-3 gene therapy improves phenotype inBrain communications · 2024Article
- AAV9-mediated SH3TC2 gene replacement therapy targeted to Schwann cells for the treatment of CMT4C.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Neuropathy due to bi-allelic SH3TC2 variants: genotype-phenotype correlation and natural history.Brain : a journal of neurology · 2023Article
- Screening for SH3TC2 variants in Charcot-Marie-Tooth disease in a cohort of Chinese patients.Acta neurologica Belgica · 2022Article
- From Negative to Positive Diagnosis: Structural Variation Could Be the Second Mutation You Are Looking for in a Recessive Autosomal Gene.Journal of personalized medicine · 2022Article
- Up-Regulation of SH3TC2 Induced by YTHDF1 Predicts Poor Outcome and Facilitates Cell-Cycle Progress in Colorectal Cancer.Journal of oncology · 2022Article
- Mechanisms and Treatments in Demyelinating CMT.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Endosomal recycling tubule scission and integrin recycling involve the membrane curvature-supporting protein LITAF.Journal of cell science · 2021Article
- Small Rab GTPases in Intracellular Vesicle Trafficking: The Case of Rab3A/Raphillin-3A Complex in the Kidney.International journal of molecular sciences · 2021Review
- Held Up in Traffic-Defects in the Trafficking Machinery in Charcot-Marie-Tooth Disease.Frontiers in molecular neuroscience · 2021Review
- Investigation of Mutations in Exon 14 ofIranian journal of child neurology · 2020Article
- Autophagic and endo-lysosomal dysfunction in neurodegenerative disease.Molecular brain · 2019Review
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Mutations in the functionally uncharacterized protein SH3TC2 are associated with the severe hereditary peripheral neuropathy, Charcot-Marie-Tooth disease type 4C (CMT4C). Similarly, to other proteins mutated in CMT, a role for SH3TC2 in endocytic membrane traffic has been previously proposed. However, recent descriptions of the intracellular localization of SH3TC2 are conflicting. Furthermore, no clear functional pathogenic mechanisms have so far been proposed to explain why both nonsense and missense mutations in SH3TC2 lead to similar clinical phenotypes. Here, we describe our intracellular localization studies, supported by biochemical and functional data, using wild-type and mutant SH3TC2. We show that wild-type SH3TC2 targets to the intracellular recycling endosome by associating with the small GTPase, Rab11, which is known to regulate the recycling of internalized membrane and receptors back to the plasma membrane. Furthermore, we demonstrate that SH3TC2 interacts preferentially with the GTP-bound form of Rab11, identifying SH3TC2 as a novel Rab11 effector. Of clinical pathological relevance, all SH3TC2 constructs harbouring disease-causing mutations are shown to be unable to associate with Rab11 with consequent loss of recycling endosome localization. Moreover, we show that wild-type SH3TC2, but not mutant SH3TC2, influences transferrin receptor dynamics, consistent with a functional role on the endocytic recycling pathway. Our data therefore implicate mistargeting of SH3TC2 away from the recycling endosome as the fundamental molecular defect that leads to CMT4C.
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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.