ArticleThe Journal of cell biology2001
Mutations in the cytoplasmic domain of P0 reveal a role for PKC-mediated phosphorylation in adhesion and myelination.
Article in The Journal of cell biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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
30 citing papers in PubMed, 87 citations in OpenAlex.
- L-MPZ, a novel isoform of myelin P0, is produced by stop codon readthrough.The Journal of biological chemistry · 2012Trial
- Disrupting the transmembrane domain interface between PMP22 and MPZ causes peripheral neuropathy.iScience · 2024Article
- Myelin protein zero mutation-related hereditary neuropathies: Neuropathological insight from a new nerve biopsy cohort.Brain pathology (Zurich, Switzerland) · 2024Article
- Homomeric interactions of the MPZ Ig domain and their relation to Charcot-Marie-Tooth disease.Brain : a journal of neurology · 2023Article
- Mechanisms and treatment strategies of demyelinating and dysmyelinating Charcot-Marie-Tooth disease.Neural regeneration research · 2023Review
- Disease Progression in Charcot-Marie-Tooth Disease Related to MPZ Mutations: A Longitudinal Study.Annals of neurology · 2023Article
- MPZ gene variant site in Chinese patients with Charcot-Marie-Tooth disease.Molecular genetics & genomic medicine · 2022Article
- Mechanisms and Treatments in Demyelinating CMT.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Genetic and clinical spectrums in Korean Charcot-Marie-Tooth disease patients with myelin protein zero mutations.Molecular genetics & genomic medicine · 2021Article
- How Does Protein Zero Assemble Compact Myelin?Cells · 2020Article
- Upregulation of large myelin protein zero leads to Charcot-Marie-Tooth disease-like neuropathy in mice.Communications biology · 2020Article
- Neuropathy-related mutations alter the membrane binding properties of the human myelin protein P0 cytoplasmic tail.PloS one · 2019Article
- A nonsense mutation in myelin protein zero causes congenital hypomyelination neuropathy through altered P0 membrane targeting and gain of abnormal function.Human molecular genetics · 2019Article
- Phylogenetically Conserved Sequences Around Myelin P0 Stop Codon are Essential for Translational Readthrough to Produce L-MPZ.Neurochemical research · 2018Article
- Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene.Brain : a journal of neurology · 2015Article
- Article
- Polarization and myelination in myelinating glia.ISRN neurology · 2012Article
- Four novel mutations of the myelin protein zero gene presenting as a mild and late-onset polyneuropathy.Journal of neurology · 2010Article
- Cellular characterization of MPZ mutations presenting with diverse clinical phenotypes.Journal of neurology · 2010Article
- Clinical features and molecular modelling of novel MPZ mutations in demyelinating and axonal neuropathies.European journal of human genetics : EJHG · 2009Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in P0 (MPZ), the major myelin protein of the peripheral nervous system, cause the inherited demyelinating neuropathy Charcot-Marie-Tooth disease type 1B. P0 is a member of the immunoglobulin superfamily and functions as a homophilic adhesion molecule. We now show that point mutations in the cytoplasmic domain that modify a PKC target motif (RSTK) or an adjacent serine residue abolish P0 adhesion function and can cause peripheral neuropathy in humans. Consistent with these data, PKCalpha along with the PKC binding protein RACK1 are immunoprecipitated with wild-type P0, and inhibition of PKC activity abolishes P0-mediated adhesion. Point mutations in the RSTK target site that abolish adhesion do not alter the association of PKC with P0; however, deletion of a 14 amino acid region, which includes the RSTK motif, does abolish the association. Thus, the interaction of PKCalpha with the cytoplasmic domain of P0 is independent of specific target residues but is dependent on a nearby sequence. We conclude that PKC-mediated phosphorylation of specific residues within the cytoplasmic domain of P0 is necessary for P0-mediated adhesion, and alteration of this process can cause demyelinating neuropathy in humans.
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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.