title: Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome.
abstract: Neurological disorders can be associated with protein glycosylation abnormalities. Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. Although its pathogenesis appears to be closely associated with a redox imbalance, no information on glycosylation is available. Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. Glycosylation changes were rescued by selected brain Mecp2 reactivation. Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5.
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy; Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Cortelazzo
authors.affiliation: Neonatal Intensive Care Unit, University Hospital, AOUS, Siena, Italy. Electronic address: degeniente@gmail.com.
authors.forename: Claudio
authors.initials: C
authors.lastname: De Felice
authors.affiliation: Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Guerranti
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Signorini
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Leoncini
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pecorelli
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy; Department of Biochemistry, Biophysics, and General Pathology, 2nd University of Naples, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Scalabrì
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Madonna
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy; Institute of Biosciences and BioResources CNR, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Filosa
authors.affiliation: Department of Life Science, University of Siena, Siena, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Della Giovampaola
authors.affiliation: Department of Life Science, University of Siena, Siena, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Capone
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS/UM/ENSCM, Montpellier, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Durand
authors.affiliation: Department of Ecological and Biological Sciences, University of Tuscia, Viterbo, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Mirasole
authors.affiliation: Department of Ecological and Biological Sciences, University of Tuscia, Viterbo, Italy.
authors.forename: Lello
authors.initials: L
authors.lastname: Zolla
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valacchi
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciccoli
authors.affiliation: The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Jacky
authors.initials: J
authors.lastname: Guy
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy; Institute of Genetics and Biophysics "Adriano Buzzati Traverso" CNR, Naples, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Esposito
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy.
authors.forename: Joussef
authors.initials: J
authors.lastname: Hayek
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D006031:Glycosylation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D008817:Mice, Mutant Strains; D011755:Pyrophosphatases / Q000378:metabolism*; D015518:Rett Syndrome / Q000378:metabolism*
chemical_list: C497393:Mecp2 protein, mouse; D008562:Membrane Glycoproteins; D051783:Methyl-CpG-Binding Protein 2; D011755:Pyrophosphatases; C000613156:nucleotide pyrophosphatase-5, mouse
keywords: Mecp2; Neurological disorders; Nucleotide pyrophosphatase; Protein glycosylation