Affinage

PMP22

Peroxisomal membrane protein 2 · UniProt Q9NR77

Length
195 aa
Mass
22.3 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PMP22 is an N-glycosylated tetraspan integral membrane glycoprotein of Schwann cells whose dosage and folding fidelity are critical determinants of peripheral nerve myelination, with point mutations causing dominant CMT1A and gene-dosage imbalance underlying CMT1A and HNPP (PMID:8510709, PMID:7581450). The protein is synthesized as an 18-kDa precursor and matured to ~22 kDa by N-linked glycosylation, and its expression is restricted to myelinating Schwann cells where it is induced by cAMP signaling (PMID:8486695, PMID:7691737), by Egr2/Sox10 acting through a conserved intronic enhancer and a distal super-enhancer that drives the Schwann cell-specific promoter (PMID:21411665, PMID:29771329), and by progesterone receptor signaling (PMID:14608378). Functionally, surface-resident wild-type PMP22 restrains Schwann cell proliferation and regulates apoptosis and cell spreading through RhoA, and controls myelin thickness and stability rather than myelin initiation (PMID:7720703, PMID:7581450, PMID:9086179, PMID:10397775, PMID:10982389). At the plasma membrane PMP22 resides in cholesterol-enriched lipid rafts and links the actin cytoskeleton to the membrane, physically partnering with ABCA1 to govern cholesterol efflux and homeostasis, and with JAM-C and MAG to maintain myelin junction integrity and permeability (PMID:24339129, PMID:25429154, PMID:31061090). PMP22 trafficking is intrinsically inefficient: conformational stability is rate-limiting for forward trafficking, with N-glycosylation at Asn41 and the ER quality-control factors calnexin, UGGT1, and RER1 acting as restraints, such that destabilizing point mutations are retained in the ER in proportion to their clinical severity, while overexpression disproportionately saturates this quality control to produce mistrafficking (PMID:15537650, PMID:26102530, PMID:32647009, PMID:33933451). Misfolded PMP22 is cleared by the proteasome, HSP70 chaperones, and autophagy, and its failure produces ubiquitinated perinuclear aggresomes (PMID:10527811, PMID:16326107, PMID:25694550). In HNPP, PMP22 haploinsufficiency disrupts myelin junctions via PAK1-driven F-actin dysregulation, impairing action potential propagation (PMID:24339129, PMID:27583434).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1993 High

    Established that PMP22 is a peripheral myelin gene whose mutation causes inherited neuropathy, defining the gene's clinical and tissue relevance.

    Evidence Point-mutation identification and co-segregation in CMT1A families; biochemical characterization of the glycoprotein in cultured Schwann cells

    PMID:7691737 PMID:8486695 PMID:8510709

    Open questions at the time
    • Did not define the cellular function of PMP22
    • Mechanism linking mutation to demyelination unknown
    • Trafficking and folding behavior uncharacterized
  2. 1995 High

    Showed that PMP22 dosage actively regulates Schwann cell proliferation, apoptosis, and myelin thickness/stability, moving it from a structural marker to a functional regulator.

    Evidence Retroviral gain/loss-of-function with BrdU and cell-cycle analysis; NIH-3T3 apoptosis assay with dominant/recessive mutant alleles; Pmp22 knockout mouse histopathology

    PMID:7581450 PMID:7649472 PMID:7720703

    Open questions at the time
    • Molecular partners mediating proliferation/apoptosis effects not identified
    • Whether effects require surface localization unresolved at this stage
  3. 1997 Medium

    Refined PMP22's role to control of myelin thickness and stability rather than myelin initiation or compaction.

    Evidence Retroviral over/under-expression in Schwann cell-DRG co-culture with EM ultrastructure

    PMID:9086179

    Open questions at the time
    • Single lab
    • Mechanism of thickness control not defined
  4. 1999 Medium

    Linked PMP22's effects on cell shape to RhoA signaling and Arf6-dependent membrane recycling, indicating cytoskeletal and trafficking-pathway engagement.

    Evidence Rho construct epistasis and C3 exoenzyme treatment; dominant-negative Arf6 and live-cell trafficking imaging

    PMID:10397775 PMID:12584243

    Open questions at the time
    • Direct biochemical interaction with Rho/Arf6 not shown
    • Relevance to in vivo myelination not established
  5. 2000 High

    Demonstrated that disease-causing missense mutants are retained in the ER and that cell-surface exposure is required for PMP22 function, establishing mislocalization as the pathogenic mechanism.

    Evidence Adenoviral expression in live rat sciatic nerve with ER marker colocalization; surface staining, ER-retrieval and N-glycosylation site mutagenesis with functional assays

    PMID:10982389 PMID:11114256

    Open questions at the time
    • Chaperones mediating retention not yet identified
    • Quantitative relationship between retention and severity not defined
  6. 2001 Medium

    Showed that PMP22 dosage and point mutations affect Schwann cell proliferation and survival specifically in later postnatal development, timing the cellular phenotype.

    Evidence BrdU, TUNEL, and density quantification across Pmp22 null, heterozygous, and overexpressing mouse nerves

    PMID:11673320

    Open questions at the time
    • Single lab
    • Molecular trigger of late-developmental effect unknown
  7. 2003 High

    Identified progesterone receptor signaling as a transcriptional regulator of Pmp22, providing a pharmacologically tractable node modulating disease severity.

    Evidence Progesterone and onapristone treatment of CMT1A transgenic rats with qRT-PCR, electrophysiology, and phenotype scoring

    PMID:14608378

    Open questions at the time
    • Direct PR binding to Pmp22 regulatory elements not mapped
    • Interaction with other transcriptional inputs unclear
  8. 2004 Medium

    Defined calnexin as a glycan-independent chaperone retaining misfolded PMP22 transmembrane domains in the ER, providing a molecular mechanism for mutant retention.

    Evidence Co-IP of calnexin with TMD-GFP fusions and live-cell FRAP

    PMID:15537650

    Open questions at the time
    • Single lab
    • Other quality-control factors not yet defined
  9. 2005 Medium

    Showed both proteasomal and autophagic degradation pathways are engaged and dysregulated in PMP22 aggregate pathology, expanding the disposal network for misfolded protein.

    Evidence Pulse-chase, proteasome activity assay, detergent fractionation, and autophagosome/lysosome immunofluorescence in CMT1A mice; earlier proteasome/aggresome study

    PMID:10527811 PMID:16326107

    Open questions at the time
    • Single lab
    • Causal contribution of each pathway to disease not separated
  10. 2011 High

    Mapped the transcriptional control of Pmp22 to an Egr2/Krox20-bound intronic enhancer requiring Sox10, defining the core Schwann cell-specific regulatory logic.

    Evidence ChIP, luciferase reporters, Sox10 manipulation, and mouse transgenic validation

    PMID:21411665

    Open questions at the time
    • Distal regulatory elements not yet identified
    • Contribution to gene-dosage disease unclear
  11. 2014 High

    Established PMP22 as a component of myelin junction complexes and lipid-raft membrane organization, identifying JAM-C, MAG, and ABCA1-relevant cholesterol pathways as effectors.

    Evidence Reciprocal Co-IP with JAM-C and MAG plus Jam-c/Mag knockout epistasis; lipid raft fractionation, F-actin staining, and cholesterol rescue in PMP22 KO Schwann cells

    PMID:24339129 PMID:25429154

    Open questions at the time
    • Stoichiometry and architecture of the junction complex unresolved
    • Direct binding interfaces not mapped
  12. 2015 High

    Quantitatively linked PMP22 conformational stability to trafficking efficiency and clinical severity, and identified HSP70 as a key chaperone preventing mutant aggregation.

    Evidence Zn(II)-mediated stability assay across 12 variants with trafficking and patient NCV correlation; HSP70 KO cells with Golgi/Rab7 colocalization and proteasome assays

    PMID:25694550 PMID:26102530

    Open questions at the time
    • Structural basis of destabilization not defined
    • HSP70 study single lab
  13. 2016 Medium

    Positioned PAK1-mediated actin polymerization upstream of myelin junction disruption in HNPP, defining a targetable effector of PMP22 haploinsufficiency.

    Evidence F-actin and PAK activity quantification with pharmacological PAK inhibition and electrophysiology in Pmp22+/- mice

    PMID:27583434

    Open questions at the time
    • Single lab
    • How PMP22 loss activates PAK1 not defined
  14. 2018 High

    Identified a distal super-enhancer required for full Pmp22 expression with promoter-specific sensitivity, refining the dosage-sensitive transcriptional architecture relevant to CMT1A/HNPP.

    Evidence CRISPR deletion of super-enhancer with allele-specific RT-qPCR and H3K27ac ChIP-seq

    PMID:29771329

    Open questions at the time
    • Transcription factors binding the super-enhancer not fully defined
    • Interaction with intronic enhancer unresolved
  15. 2019 High

    Established a reciprocal physical and functional partnership between PMP22 and ABCA1 governing Schwann cell cholesterol efflux and homeostasis.

    Evidence Reciprocal Co-IP, colocalization, cholesterol efflux and patch-clamp assays in PMP22 KO and ABCA1 KO mice

    PMID:31061090

    Open questions at the time
    • Direct binding interface unmapped
    • Whether the interaction is altered by disease mutants untested
  16. 2021 High

    Dissected the ER quality-control machinery restraining PMP22 trafficking and showed overexpression saturates this control, unifying point-mutation and gene-dosage mechanisms.

    Evidence Single-cell flow trafficking assays, N41Q mutagenesis, OST-A/B depletion, CRISPR KO of RER1/UGGT1/calnexin, and interactome proteomics

    PMID:32647009 PMID:33933451

    Open questions at the time
    • In vivo relevance of glycosylation-limited trafficking not tested
    • Structural reason for inherent inefficiency unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct PMP22 partner complexes (ABCA1, JAM-C/MAG, lipid rafts) are coordinated at the Schwann cell membrane and whether modulating trafficking efficiency can therapeutically rescue myelination remains unresolved.
  • No integrated structural model of PMP22 membrane complexes
  • Whether enhancing forward trafficking corrects disease phenotypes in vivo untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0008092 cytoskeletal protein binding 2 GO:0098631 cell adhesion mediator activity 1
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005886 plasma membrane 3 GO:0005768 endosome 1
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1266738 Developmental Biology 2
Partners
ABCA1CALNEXINHSP70JAM-CMAGRER1UGGT1
Complex memberships
myelin junction complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 PMP22 encodes a peripheral myelin protein; a point mutation (Ser→Cys) in a putative transmembrane domain causes CMT1A in an autosomal dominant pattern, establishing a causative role for PMP22 in peripheral nerve myelination. PCR, heteroduplex analysis, direct nucleotide sequencing of patient DNA; co-segregation analysis The New England journal of medicine High 8510709
1993 In cultured Schwann cells, PMP22 is synthesized from an 18-kDa precursor and post-translationally modified by N-linked glycosylation, yielding the mature ~22 kDa glycoprotein; PMP22 mRNA (1.8 kb) is upregulated by forskolin (cAMP pathway activation). Metabolic labeling, immunoprecipitation with anti-PMP22 antibodies, N-glycosylation analysis, Northern blot, Western blot of purified myelin after deglycosylation The Journal of biological chemistry High 8486695
1993 PMP22 mRNA expression in peripheral nerve is restricted to Schwann cells of myelinated fibers and is co-expressed with MBP and P0 during developmental myelination and nerve regeneration; in cultured Schwann cells PMP22 expression is not strictly growth-arrest-specific (unlike in fibroblasts). In situ hybridization, immunohistochemistry, Northern blot of cultured Schwann cells under different growth conditions Glia Medium 7691737
1995 Retroviral-mediated overexpression of PMP22 in Schwann cells decreases DNA synthesis to ~60% of control and delays G0/G1→S+G2/M entry by ~8 h; antisense-mediated reduction of PMP22 increases DNA synthesis to ~150%, demonstrating that PMP22 directly regulates Schwann cell proliferation. Retroviral transduction (sense/antisense), BrdU incorporation, flow cytometry cell cycle analysis The EMBO journal High 7720703
1995 Overexpression of wild-type Gas3/PMP22 in NIH-3T3 cells induces an apoptotic-like phenotype (membrane blebbing, rounding, chromatin condensation without DNA fragmentation) suppressible by antioxidants. CMT1A dominant point mutants (L16P, S79C) behave as dominant negatives for this apoptotic activity; the recessive mutant T118M behaves recessively, establishing PMP22 as a regulator of apoptosis. Transient transfection overexpression in NIH-3T3 cells; morphological analysis; antioxidant rescue; co-expression dominant-negative experiments Genes & development Medium 7649472
1995 Mice homozygously deleted for Pmp22 show delayed onset of myelination, formation of tomacula (sausage-like hypermyelination), severe demyelination, axonal loss, and functional impairment; heterozygous Pmp22+/- mice exhibit focal tomacula resembling HNPP, establishing Pmp22 as required for correct peripheral nerve development, myelin thickness determination, and myelin stability. Targeted gene disruption (knockout mice), histopathology, morphometry, electrophysiology Nature genetics High 7581450
1997 Altered PMP22 expression (over- or under-expression via retroviral transduction) in Schwann cells co-cultured with DRG neurons does not impair early myelination or membrane compaction but affects myelin thickness and stability, indicating PMP22's role is in controlling myelin thickness rather than initiation of myelination. Retroviral transduction of Schwann cells, co-culture with DRG neurons, RT-PCR, immunohistochemistry, confocal microscopy, electron microscopy Journal of neuroscience research Medium 9086179
1999 Gas3/PMP22 overexpression modulates cell spreading through the small GTPase RhoA: active RhoA counteracts Gas3/PMP22-dependent morphological changes but not apoptosis; C3 exoenzyme (Rho inhibitor) renders otherwise unresponsive REF52 cells susceptible to Gas3/PMP22-induced shape changes; Gas3/PMP22 impairs LPA-induced stress fiber and focal adhesion assembly. Transfection with active/dominant-negative Rho constructs, C3 exoenzyme treatment, cytotoxic necrotizing factor 1 activation of endogenous Rho, time-lapse imaging, Bcl-2 co-expression Molecular biology of the cell Medium 10397775
1999 Inhibition of the proteasome pathway causes accumulation of PMP22 in perinuclear aggresomes (co-labeled with ubiquitin); overexpression of PMP22 in Schwann cells alone can induce perinuclear accumulation, establishing that the proteasome pathway is critical for regulating PMP22 protein levels. Proteasome inhibitor treatment, immunofluorescence double-labeling with anti-ubiquitin and organelle markers, confocal microscopy Neurobiology of disease Medium 10527811
2000 Trembler (Tr) and Trembler-J (Tr-J) point-mutant PMP22 proteins are retained in the endoplasmic reticulum (ER) of myelinating Schwann cells in vivo, while wild-type epitope-tagged PMP22 is successfully transported to compact myelin, demonstrating that missense mutations cause pathogenesis through ER retention. Adenoviral microinjection into sciatic nerve of live rats; immunohistochemistry with ER marker colocalization in myelinating Schwann cells Neurobiology of disease High 11114256
2000 Wild-type Gas3/PMP22 is exposed at the cell surface, whereas disease-causing point mutants are intracellularly retained co-localizing with ER. Cell-surface exposure is required for Gas3/PMP22 to regulate both cell death and cell spreading; addition of a retrieval signal to wild-type prevents surface exposure and abolishes both functions. N-glycosylation (Asn41) is required for full cell-spreading effect but not for cell death induction. Immunofluorescence surface staining, ER co-localization, mutagenesis of ER-retrieval motif and N-glycosylation site, cell death and spreading assays Molecular biology of the cell High 10982389
2001 Increased Schwann cell proliferation and apoptosis appear in later postnatal development in all PMP22 mutant mouse models (overexpression, deletion, point mutation), but not at P1, demonstrating that PMP22 dosage and point mutations affect Schwann cell proliferation and survival primarily in later development. BrdU labeling (proliferation), TUNEL/cleaved caspase (apoptosis), cell density quantification in postnatal sciatic nerve of Pmp22 null, heterozygous, and overexpressing mice Brain : a journal of neurology Medium 11673320
2003 Progesterone directly regulates Pmp22 and Mpz mRNA levels in Schwann cells: progesterone administration elevates Pmp22 and Mpz mRNA in sciatic nerve and worsens CMT1A phenotype; a progesterone receptor antagonist (onapristone) reduces Pmp22 overexpression and improves the neuropathy phenotype in transgenic CMT1A rats, demonstrating progesterone receptor-mediated transcriptional regulation of PMP22 in Schwann cells. Pharmacological treatment in transgenic rats; qRT-PCR of Pmp22/Mpz mRNA; electrophysiology; clinical phenotype assessment Nature medicine High 14608378
2004 Calnexin interacts with misfolded transmembrane domains of Gas3/PMP22 in a glycan-independent manner, retaining mutant PMP22 in the ER; FRAP experiments show PMP22 disease mutants are mobile but diffuse at ~half the diffusion coefficient of wild-type, consistent with chaperone-mediated retention. Co-immunoprecipitation of calnexin with PMP22 transmembrane domain-GFP fusions; FRAP (fluorescence recovery after photobleaching) in live cells; glycan-independent interaction confirmed by mutation The Journal of biological chemistry Medium 15537650
2003 Gas3/PMP22 overexpression alters membrane traffic through the Arf6 plasma membrane-endosomal recycling pathway: overexpressed PMP22 accumulates in late endosomes and induces formation of actin/PIP2-positive vacuoles trapping Arf6-pathway membrane proteins; dominant-negative Arf6-T27N blocks vacuole formation; a CMT1A point mutant fails to trigger PIP2-positive vacuole accumulation. Live-cell imaging of GFP-tagged proteins, dominant-negative and constitutively active Arf6 constructs, transferrin receptor trafficking assay, immunofluorescence co-localization Journal of cell science Medium 12584243
2005 In CMT1A (C22) mice overexpressing PMP22, newly synthesized PMP22 shows slowed turnover, cytoplasmic protein aggregates form with reduced proteasome activity, accumulation of detergent-insoluble ubiquitinated substrates, and a fraction of aggregates associates with autophagosomes and lysosomes, indicating that dysregulation of both proteasomal and autophagic degradation pathways underlies PMP22 aggregate pathology. Pulse-chase metabolic labeling, proteasome activity assay, detergent fractionation/Western blot for ubiquitinated proteins, immunofluorescence with autophagosome/lysosome markers Neurobiology of disease Medium 16326107
2011 The Egr2/Krox20 transcription factor binds a conserved intronic enhancer (~250 bp) within the largest intron of the Pmp22 gene; Sox10 is required for optimal activity of this intronic site and for PMP22 expression; mouse transgenic analysis confirms tissue-specific (peripheral nerve) activity of this intronic sequence. Chromatin immunoprecipitation (ChIP) of rat Pmp22 locus, luciferase reporter assays, Sox10 knockdown/expression assays, mouse transgenic analysis The Journal of neuroscience High 21411665
2014 PMP22 interacts physically with junctional adhesion molecule-C (JAM-C) and myelin-associated glycoprotein (MAG); PMP22 deficiency disrupts multiple myelin junction complexes, causing increased myelin permeability and impaired action potential propagation. Deletion of Jam-c or Mag individually recapitulates HNPP pathology, establishing PMP22 as a component of myelin junction complexes. Co-immunoprecipitation of PMP22 with JAM-C and MAG from nerve lysates; morphological analysis of junction complexes; electrophysiological assays; Jam-c and Mag knockout mouse genetic epistasis Annals of neurology High 24339129
2014 PMP22 is localized to cholesterol-enriched lipid raft membrane domains; PMP22-deficient Schwann cells show impaired migration and adhesion, shortened myelin internodes, collapsed lamellipodia, and failure of F-actin-enriched Schmidt-Lanterman incisures to form properly; expression and localization of flotillin-1, cholesterol, and GM1 ganglioside are altered. Cholesterol supplementation rescues elongation and migration deficits, linking PMP22 to actin cytoskeleton-plasma membrane linkage via lipid raft cholesterol regulation. Schwann cell migration/adhesion assays with PMP22 KO cells, phalloidin staining of F-actin, lipid raft fractionation, immunofluorescence for flotillin-1/GM1/cholesterol; cholesterol supplementation rescue The Journal of neuroscience High 25429154
2015 The conformational stability of PMP22 (assessed by Zn(II)-mediated folding equilibrium) is proportional to the efficiency of its cellular trafficking through the secretory pathway; disease-causing mutations destabilize PMP22 and reduce trafficking efficiency proportionally to reductions in motor nerve conduction velocity in patients, establishing that misfolding-driven ER retention is the molecular basis for CMT from PMP22 point mutations. Quantitative Zn(II)-mediated conformational stability assay for 12 PMP22 variants, flow-cytometry-based cellular trafficking assay, correlation with patient NCV data Journal of the American Chemical Society High 26102530
2015 Inducible HSP70 (HSP70.1/3) is critical for preventing aggregation of misfolded PMP22 (especially Trembler-J PMP22) under proteotoxic stress; HSP70 aids processing of Tr-J PMP22 through the Golgi and delivery to lysosomes via Rab7-positive vesicles; HSP70 KO cells show increased PMP22 aggregation and proteasome dysfunction. HSP70.1/3 knockout mouse-derived cells, pharmacological induction of HSP70 (FDA-approved small molecule), immunofluorescence co-localization with Golgi/Rab7 markers, proteasome activity assay, Western blot ASN neuro Medium 25694550
2016 In Pmp22+/- (HNPP model) nerves, increased F-actin levels correlate with enhanced PAK1 activity; pharmacological PAK inhibition normalizes F-actin, prevents progression of myelin junction disruption, and prevents nerve conduction failure, positioning PAK1-mediated actin polymerization upstream of myelin junction disruption in HNPP. Immunofluorescence quantification of F-actin in nerve sections, PAK kinase activity assay, pharmacological PAK inhibitor treatment in Pmp22+/- mice, electrophysiology PLoS genetics Medium 27583434
2018 A distal super-enhancer (~90-130 kb upstream of Pmp22 TSS) is required for full Pmp22 expression; CRISPR deletion of this super-enhancer significantly decreases Pmp22 transcript levels, with the Schwann cell-specific P1 promoter being disproportionately more sensitive than the P2 promoter. Genome editing (CRISPR) deletion of super-enhancer, allele-specific RT-qPCR, H3K27ac ChIP-seq chromatin mark identification Human molecular genetics High 29771329
2019 PMP22 co-immunoprecipitates with ABCA1 from Schwann cell and nerve lysates, and both proteins co-localize at the Schwann cell plasma membrane; PMP22 absence reduces ABCA1 membrane localization and impairs ABCA1-mediated cholesterol efflux. Conversely, ABCA1 KO mice show elevated PMP22 expression with aberrant subcellular processing, establishing a reciprocal functional interaction between PMP22 and ABCA1 in cholesterol homeostasis. Co-immunoprecipitation from Schwann cell/nerve lysates, immunofluorescence co-localization, cholesterol efflux assay, whole-cell patch-clamp (membrane capacitance/resistance), Western blot in PMP22 KO and ABCA1 KO mice The Journal of neuroscience High 31061090
2020 As the expression level of PMP22 (wild-type or disease variants) is increased in individual cells, the fraction of intracellularly retained (misfolded) PMP22 increases disproportionately relative to surface-trafficked protein, demonstrating that overexpression per se saturates ER quality control to produce mistrafficking. Single-cell flow-cytometry trafficking assay distinguishing surface vs. intracellular PMP22; stable and transient expression systems The Journal of biological chemistry Medium 32647009
2021 N-glycosylation at Asn41 is a limiting factor for forward trafficking of PMP22: N41Q mutation increases wild-type trafficking efficiency ~3-fold and L16P ~10-fold in HEK293 and Schwann cells. WT PMP22 is glycosylated post-translationally by OST-B; L16P is co-translationally glycosylated by OST-A. CRISPR KO studies identify RER1 as limiting for all PMP22 forms, UGGT1 as limiting for WT and L16P but not N41Q, and calnexin as limiting for WT and N41Q but not L16P. N41Q mutagenesis, flow-cytometry trafficking assay, OST-A/B depletion, CRISPR KO of RER1/UGGT1/calnexin, quantitative proteomics interactome screens The Journal of biological chemistry High 33933451

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Charcot-Marie-Tooth disease type 1A. Association with a spontaneous point mutation in the PMP22 gene. The New England journal of medicine 333 8510709
1995 Hypermyelination and demyelinating peripheral neuropathy in Pmp22-deficient mice. Nature genetics 328 7581450
2000 PERP, an apoptosis-associated target of p53, is a novel member of the PMP-22/gas3 family. Genes & development 305 10733530
2003 Therapeutic administration of progesterone antagonist in a model of Charcot-Marie-Tooth disease (CMT-1A). Nature medicine 219 14608378
2012 The PMP22 gene and its related diseases. Molecular neurobiology 213 23224996
1995 Retroviral-mediated gene transfer of the peripheral myelin protein PMP22 in Schwann cells: modulation of cell growth. The EMBO journal 174 7720703
2003 Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients. Brain : a journal of neurology 172 12477701
1993 Evidence for a recessive PMP22 point mutation in Charcot-Marie-Tooth disease type 1A. Nature genetics 168 8252046
1995 Apoptotic phenotype induced by overexpression of wild-type gas3/PMP22: its relation to the demyelinating peripheral neuropathy CMT1A. Genes & development 157 7649472
2005 NT-3 promotes nerve regeneration and sensory improvement in CMT1A mouse models and in patients. Neurology 143 16157899
2014 PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies. Orphanet journal of rare diseases 135 24646194
2017 PMP22 antisense oligonucleotides reverse Charcot-Marie-Tooth disease type 1A features in rodent models. The Journal of clinical investigation 127 29202483
1999 PMP22 accumulation in aggresomes: implications for CMT1A pathology. Neurobiology of disease 126 10527811
1997 Diagnosis of CMT1A duplications and HNPP deletions by interphase FISH: implications for testing in the cytogenetics laboratory. American journal of medical genetics 119 9096765
2001 The 1.4-Mb CMT1A duplication/HNPP deletion genomic region reveals unique genome architectural features and provides insights into the recent evolution of new genes. Genome research 116 11381029
1993 Detection and processing of peripheral myelin protein PMP22 in cultured Schwann cells. The Journal of biological chemistry 109 8486695
2005 Alterations in degradative pathways and protein aggregation in a neuropathy model based on PMP22 overexpression. Neurobiology of disease 105 16326107
1998 Many facets of the peripheral myelin protein PMP22 in myelination and disease. Microscopy research and technique 104 9672419
2010 Mechanisms for nonrecurrent genomic rearrangements associated with CMT1A or HNPP: rare CNVs as a cause for missing heritability. American journal of human genetics 101 20493460
2001 The evolutionary chromosome translocation 4;19 in Gorilla gorilla is associated with microduplication of the chromosome fragment syntenic to sequences surrounding the human proximal CMT1A-REP. Genome research 81 11435402
2000 PMP22 carrying the trembler or trembler-J mutation is intracellularly retained in myelinating Schwann cells. Neurobiology of disease 76 11114256
2002 Comparison of a new pmp22 transgenic mouse line with other mouse models and human patients with CMT1A. Journal of anatomy 74 12090404
2001 Regulation of Schwann cell proliferation and apoptosis in PMP22-deficient mice and mouse models of Charcot-Marie-Tooth disease type 1A. Brain : a journal of neurology 72 11673320
2014 Polytherapy with a combination of three repurposed drugs (PXT3003) down-regulates Pmp22 over-expression and improves myelination, axonal and functional parameters in models of CMT1A neuropathy. Orphanet journal of rare diseases 71 25491744
1998 Fine mapping of de novo CMT1A and HNPP rearrangements within CMT1A-REPs evidences two distinct sex-dependent mechanisms and candidate sequences involved in recombination. Human molecular genetics 71 9384615
1998 Charcot-Marie-Tooth disease: histopathological features of the peripheral myelin protein (PMP22) duplication (CMT1A) and connexin32 mutations (CMTX1). Muscle & nerve 65 9466597
2002 PMP22 overexpression causes dysmyelination in mice. Brain : a journal of neurology 64 12244079
1999 Rho-dependent regulation of cell spreading by the tetraspan membrane protein Gas3/PMP22. Molecular biology of the cell 64 10397775
1993 Coexpression of PMP22 gene with MBP and P0 during de novo myelination and nerve repair. Glia 64 7691737
1995 Analysis of the CMT1A-REP repeat: mapping crossover breakpoints in CMT1A and HNPP. Human molecular genetics 60 8634706
2009 Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal models. Neurogenetics 58 19290556
2009 PMP22 expression in dermal nerve myelin from patients with CMT1A. Brain : a journal of neurology 58 19447823
2014 Abnormal junctions and permeability of myelin in PMP22-deficient nerves. Annals of neurology 57 24339129
2013 Regulation of PMP22 mRNA by G3BP1 affects cell proliferation in breast cancer cells. Molecular cancer 57 24321297
2009 P2X7-mediated increased intracellular calcium causes functional derangement in Schwann cells from rats with CMT1A neuropathy. The Journal of biological chemistry 57 19546221
1999 A unique point mutation in the PMP22 gene is associated with Charcot-Marie-Tooth disease and deafness. American journal of human genetics 57 10330345
1998 Pathogenesis of Charcot-Marie-Tooth 1A (CMT1A) neuropathy. Trends in neurosciences 55 9683317
1997 Detection of the CMT1A/HNPP recombination hotspot in unrelated patients of European descent. Journal of medical genetics 55 9032649
2014 PMP22 is critical for actin-mediated cellular functions and for establishing lipid rafts. The Journal of neuroscience : the official journal of the Society for Neuroscience 54 25429154
2010 Conduction block in PMP22 deficiency. The Journal of neuroscience : the official journal of the Society for Neuroscience 54 20071523
2006 T118M PMP22 mutation causes partial loss of function and HNPP-like neuropathy. Annals of neurology 54 16437560
2003 A new quantitative PCR multiplex assay for rapid analysis of chromosome 17p11.2-12 duplications and deletions leading to HMSN/HNPP. European journal of human genetics : EJHG 54 12634865
1996 Ultrastructural distribution of PMP22 in Charcot-Marie-Tooth disease type 1A. Journal of neuropathology and experimental neurology 54 8786387
1995 Identification and characterization of a novel squamous cell-associated gene related to PMP22. The Journal of biological chemistry 52 7499420
2011 Regulation of the PMP22 gene through an intronic enhancer. The Journal of neuroscience : the official journal of the Society for Neuroscience 51 21411665
2021 Squalenoyl siRNA PMP22 nanoparticles are effective in treating mouse models of Charcot-Marie-Tooth disease type 1 A. Communications biology 50 33750896
2004 Improved testing for CMT1A and HNPP using multiplex ligation-dependent probe amplification (MLPA) with rapid DNA preparations: comparison with the interphase FISH method. Human mutation 50 15241798
2015 Conformational Stability and Pathogenic Misfolding of the Integral Membrane Protein PMP22. Journal of the American Chemical Society 48 26102530
2022 A translatable RNAi-driven gene therapy silences PMP22/Pmp22 genes and improves neuropathy in CMT1A mice. The Journal of clinical investigation 47 35579942
1997 Schwann cell differentiation in Charcot-Marie-Tooth disease type 1A (CMT1A): normal number of myelinating Schwann cells in young CMT1A patients and neural cell adhesion molecule expression in onion bulbs. Acta neuropathologica 45 9341930
2019 PMP22 Regulates Cholesterol Trafficking and ABCA1-Mediated Cholesterol Efflux. The Journal of neuroscience : the official journal of the Society for Neuroscience 43 31061090
2000 Molecular dissection of the Schwann cell specific promoter of the PMP22 gene. Gene 43 10806367
1999 Homologous DNA exchanges in humans can be explained by the yeast double-strand break repair model: a study of 17p11.2 rearrangements associated with CMT1A and HNPP. Human molecular genetics 41 10545609
1998 A novel PMP22 point mutation causing HNPP phenotype: studies on nerve xenografts. Neurology 41 9748013
2017 PMP22 Regulates Self-Renewal and Chemoresistance of Gastric Cancer Cells. Molecular cancer therapeutics 40 28336807
1997 Studies on the effects of altered PMP22 expression during myelination in vitro. Journal of neuroscience research 40 9086179
2009 Copy number variation upstream of PMP22 in Charcot-Marie-Tooth disease. European journal of human genetics : EJHG 39 19888301
2000 Exposure at the cell surface is required for gas3/PMP22 To regulate both cell death and cell spreading: implication for the Charcot-Marie-Tooth type 1A and Dejerine-Sottas diseases. Molecular biology of the cell 39 10982389
1996 Low affinity NGF receptor expression in CMT1A nerve biopsies of different disease stages. Brain : a journal of neurology 39 8931571
2012 Identification of drug modulators targeting gene-dosage disease CMT1A. ACS chemical biology 38 22530759
1996 Deletion of the PMP22 gene and hereditary neuropathy with liability to pressure palsies. Current opinion in neurology 37 8894410
2022 Treatment with IFB-088 Improves Neuropathy in CMT1A and CMT1B Mice. Molecular neurobiology 35 35501630
2019 Transmembrane protease serine 5: a novel Schwann cell plasma marker for CMT1A. Annals of clinical and translational neurology 35 31833243
2017 Pmp22 mutant allele-specific siRNA alleviates demyelinating neuropathic phenotype in vivo. Neurobiology of disease 35 28108290
1998 Fate of Schwann cells in CMT1A and HNPP: evidence for apoptosis. Journal of neuropathology and experimental neurology 33 9630241
2004 Glycan-independent role of calnexin in the intracellular retention of Charcot-Marie-tooth 1A Gas3/PMP22 mutants. The Journal of biological chemistry 32 15537650
2020 MiR-139-5p negatively regulates PMP22 to repress cell proliferation by targeting the NF-κB signaling pathway in gastric cancer. International journal of biological sciences 31 32174796
2019 miR-381 Attenuates Peripheral Neuropathic Phenotype Caused by Overexpression of PMP22. Experimental neurobiology 31 31138995
2003 Alterations in the Arf6-regulated plasma membrane endosomal recycling pathway in cells overexpressing the tetraspan protein Gas3/PMP22. Journal of cell science 31 12584243
1998 Determination of gene dosage at the PMP22 and androgen receptor loci by quantitative PCR. Clinical chemistry 30 9554482
2020 Treating PMP22 gene duplication-related Charcot-Marie-Tooth disease: the past, the present and the future. Translational research : the journal of laboratory and clinical medicine 29 32693030
2002 Identification of a new Pmp22 mouse mutant and trafficking analysis of a Pmp22 allelic series suggesting that protein aggregates may be protective in Pmp22-associated peripheral neuropathy. Molecular and cellular neurosciences 29 12359155
2019 Regulating PMP22 expression as a dosage sensitive neuropathy gene. Brain research 28 31586623
2023 Downregulation of PMP22 ameliorates myelin defects in iPSC-derived human organoid cultures of CMT1A. Brain : a journal of neurology 27 36511878
2016 Tolerability and efficacy study of P2X7 inhibition in experimental Charcot-Marie-Tooth type 1A (CMT1A) neuropathy. Neurobiology of disease 27 27431093
2016 Tuning PAK Activity to Rescue Abnormal Myelin Permeability in HNPP. PLoS genetics 27 27583434
2013 Claudins reign: The claudin/EMP/PMP22/γ channel protein family in C. elegans. Tissue barriers 27 24665403
2000 Mutational analysis and genotype/phenotype correlation in Turkish Charcot-Marie-Tooth Type 1 and HNPP patients. Clinical genetics 27 11140841
1999 Distinct Phenotypes Associated with Increasing Dosage of the PLP Gene: Implications for CMT1A Due to PMP22 Gene Duplication. Annals of the New York Academy of Sciences 26 29086937
1999 Molecular Mechanisms for CMT1A Duplication and HNPP Deletion. Annals of the New York Academy of Sciences 26 29086952
2000 Tetraspan myelin protein PMP22 and demyelinating peripheral neuropathies: new facts and hypotheses. Glia 25 10625337
2015 Inducible HSP70 is critical in preventing the aggregation and enhancing the processing of PMP22. ASN neuro 24 25694550
2015 Molecular and clinical features of inherited neuropathies due to PMP22 duplication. Journal of the neurological sciences 24 26076881
2007 Rapid diagnosis of CMT1A duplications and HNPP deletions by multiplex microsatellite PCR. Molecules and cells 24 17464210
2023 CMT1A current gene therapy approaches and promising biomarkers. Neural regeneration research 23 36571339
2020 Direct relationship between increased expression and mistrafficking of the Charcot-Marie-Tooth-associated protein PMP22. The Journal of biological chemistry 23 32647009
2014 PMP22 messenger RNA levels in skin biopsies: testing the effectiveness of a Charcot-Marie-Tooth 1A biomarker. Brain : a journal of neurology 23 24812204
2014 Mutation analysis of MFN2, GJB1, MPZ and PMP22 in Italian patients with axonal Charcot-Marie-Tooth disease. Neuromolecular medicine 23 24819634
2021 Glycosylation limits forward trafficking of the tetraspan membrane protein PMP22. The Journal of biological chemistry 22 33933451
2018 Regulation of the neuropathy-associated Pmp22 gene by a distal super-enhancer. Human molecular genetics 22 29771329
2017 Caveats in the Established Understanding of CMT1A. Annals of clinical and translational neurology 22 28812050
2004 Characterization of PMP22 expression in osteosarcoma. Cancer genetics and cytogenetics 22 15262428
2001 PMP22 transgenic dorsal root ganglia cultures show myelin abnormalities similar to those of human CMT1A. Annals of neurology 21 11456309
1999 Expression analysis of the PMP22 gene in glioma and osteogenic sarcoma cell lines. Journal of neuroscience research 21 10561690
1999 Transgenic Mouse Models of CMT1A and HNPP. Annals of the New York Academy of Sciences 21 29086924
1997 Locations of crossover breakpoints within the CMT1A-REP repeat in Japanese patients with CMT1A and HNPP. Human genetics 21 9048912
2015 The Functional Role of PMP22 Gene in the Proliferation and Invasion of Osteosarcoma. Medical science monitor : international medical journal of experimental and clinical research 20 26154129
2011 Neuropathy in a human without the PMP22 gene. Archives of neurology 20 21670407
2024 PMP22 duplication dysregulates lipid homeostasis and plasma membrane organization in developing human Schwann cells. Brain : a journal of neurology 19 38743588
2021 Dysregulated miR-29a-3p/PMP22 Modulates Schwann Cell Proliferation and Migration During Peripheral Nerve Regeneration. Molecular neurobiology 19 34837628

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