ArticleThe Journal of biological chemistry2013
Depletion of molecular chaperones from the endoplasmic reticulum and fragmentation of the Golgi apparatus associated with pathogenesis in Pelizaeus-Merzbacher disease.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- Beyond Neurodegeneration: White Matter Vacuolation as a Primary Myelin Defect.International journal of molecular sciences · 2026Review
- Review
- Spatially concentrated adenine base editors efficiently correct PLP1 mutations in oligodendrocytes.Nucleic acids research · 2026Article
- Pelizaeus-Merzbacher disease: on the cusp of myelin medicine.Trends in molecular medicine · 2024Review
- Emerging Evidence of Golgi Stress Signaling for Neuropathies.Neurology international · 2024Review
- Alterations in oligodendrocyte transcriptional networks reveal region-specific vulnerabilities to neurological disease.iScience · 2023Article
- KDEL Receptors: Pathophysiological Functions, Therapeutic Options, and Biotechnological Opportunities.Biomedicines · 2022Review
- Calnexin Depletion by Endoplasmic Reticulum Stress During Cholestasis Inhibits the NaHepatology communications · 2018Article
- Chemical Screening Identifies Enhancers of Mutant Oligodendrocyte Survival and Unmasks a Distinct Pathological Phase in Pelizaeus-Merzbacher Disease.Stem cell reports · 2018Article
- Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms.Acta neuropathologica · 2017Review
- Modeling the Mutational and Phenotypic Landscapes of Pelizaeus-Merzbacher Disease with Human iPSC-Derived Oligodendrocytes.American journal of human genetics · 2017Article
- The Role of BiP Retrieval by the KDEL Receptor in the Early Secretory Pathway and its Effect on Protein Quality Control and Neurodegeneration.Frontiers in molecular neuroscience · 2017Review
- Cellular Pathology of Pelizaeus-Merzbacher Disease Involving Chaperones Associated with Endoplasmic Reticulum Stress.Frontiers in molecular biosciences · 2017Review
- Golgi fragmentation induced by heat shock or inhibition of heat shock proteins is mediated by non-muscle myosin IIA via its interaction with glycosyltransferases.Cell stress & chaperones · 2014Article
- Human diseases associated with form and function of the Golgi complex.International journal of molecular sciences · 2013Review
- Golgi tubules: their structure, formation and role in intra-Golgi transport.Histochemistry and cell biology · 2013Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Missense mutations in the proteolipid protein 1 (PLP1) gene cause a wide spectrum of hypomyelinating disorders, from mild spastic paraplegia type 2 to severe Pelizaeus-Merzbacher disease (PMD). Mutant PLP1 accumulates in the endoplasmic reticulum (ER) and induces ER stress. However, the link between the clinical severity of PMD and the cellular response induced by mutant PLP1 remains largely unknown. Accumulation of misfolded proteins in the ER generally leads to up-regulation of ER chaperones to alleviate ER stress. Here, we found that expression of the PLP1-A243V mutant, which causes severe disease, depletes some ER chaperones with a KDEL (Lys-Asp-Glu-Leu) motif, in HeLa cells, MO3.13 oligodendrocytic cells, and primary oligodendrocytes. The same PLP1 mutant also induces fragmentation of the Golgi apparatus (GA). These organelle changes are less prominent in cells with milder disease-associated PLP1 mutants. Similar changes are also observed in cells expressing another disease-causing gene that triggers ER stress, as well as in cells treated with brefeldin A, which induces ER stress and GA fragmentation by inhibiting GA to ER trafficking. We also found that mutant PLP1 disturbs localization of the KDEL receptor, which transports the chaperones with the KDEL motif from the GA to the ER. These data show that PLP1 mutants inhibit GA to ER trafficking, which reduces the supply of ER chaperones and induces GA fragmentation. We propose that depletion of ER chaperones and GA fragmentation induced by mutant misfolded proteins contribute to the pathogenesis of inherited ER stress-related diseases and affect the disease severity.
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