A Gain-of-Glycosylation Mutation Associated with Myoclonus-Dystonia Syndrome Affects Trafficking and Processing of Mouse epsilon-Sarcoglycan in the Late Secretory Pathway (Articolo in rivista)

Type

• Prodotto della ricerca (Classe)
• Articolo in rivista (Classe)

Label

• A Gain-of-Glycosylation Mutation Associated with Myoclonus-Dystonia Syndrome Affects Trafficking and Processing of Mouse epsilon-Sarcoglycan in the Late Secretory Pathway (Articolo in rivista) (literal)

Anno

• 2011-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1002/humu.21561 (literal)

Alternative label

• Waite, Adrian; De Rosa, Maria Cristina; Brancaccio, Andrea; Blake, Derek J. (2011)
  A Gain-of-Glycosylation Mutation Associated with Myoclonus-Dystonia Syndrome Affects Trafficking and Processing of Mouse epsilon-Sarcoglycan in the Late Secretory Pathway
  in Human mutation
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Waite, Adrian; De Rosa, Maria Cristina; Brancaccio, Andrea; Blake, Derek J. (literal)

Pagina inizio

• 1246 (literal)

Pagina fine

• 1258 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 32 (literal)

Rivista

• Human mutation (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

• 13 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

• 11 (literal)

Note

• ISI Web of Science (WoS) (literal)
• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Cardiff University; University of Oxford; Catholic University of the Sacred Heart (literal)

Titolo

• A Gain-of-Glycosylation Mutation Associated with Myoclonus-Dystonia Syndrome Affects Trafficking and Processing of Mouse epsilon-Sarcoglycan in the Late Secretory Pathway (literal)

Abstract

• Missense mutations in the SGCE gene encoding epsilon-sarcoglycan account for approximately 15% of SGCE-positive cases of myoclonus-dystonia syndrome (MDS) in humans. In this study, we show that while the majority of MDS-associated missense mutants modeled with a murine epsilon-sarcoglycan cDNA are substrates for endoplasmic reticulum-associated degradation, one mutant, M68T (analogous to human c.275T>C, p.M92T), located in the Ig-like domain of epsilon-sarcoglycan, results in a gain-of-glycosylation mutation producing a protein that is targeted to the plasma membrane, albeit at reduced levels compared to wild-type epsilon-sarcoglycan. Removal of the ectopic N-linked glycan failed to restore efficient plasma membrane targeting of M68T demonstrating that the substitution rather than the glycan was responsible for the trafficking defect of this mutant. M68T also colocalized with CD63-positive vesicles in the endosomal-lysosomal system and was found to be more susceptible to lysosomal proteolysis than wild-type epsilon-sarcoglycan. Finally, we demonstrate impaired ectodomain shedding of M68T, a process that occurs physiologically for epsilon-sarcoglycan resulting in the lysosomal trafficking of the intracellular C-terminal domain of the protein. Our findings show that functional analysis of rare missense mutations can provide a mechanistic insight into the pathogenesis of MDS and the physiological role of epsilon-sarcoglycan. Hum Mutat 32: 1246-1258, 2011. (C) 2011 Wiley Periodicals, Inc. (literal)

Prodotto di

• Istituto di chimica del riconoscimento molecolare (ICRM) (Istituto)
• Modellistica molecolare di proteine legate a processi patologici (PM.P01.026.002) (Modulo)

Autore CNR

• ANDREA BRANCACCIO (Unità di personale interno)
• MARIA CRISTINA DE ROSA (Persona)

Insieme di parole chiave

• Parole chiave di "A Gain-of-Glycosylation Mutation Associated with Myoclonus-Dystonia Syndrome Affects Trafficking and Processing of Mouse epsilon-Sarcoglycan in the Late Secretory Pathway" (Insieme di parole chiave)

Incoming links:

Autore CNR di

• MARIA CRISTINA DE ROSA (Persona)
• ANDREA BRANCACCIO (Unità di personale interno)

Prodotto

• Istituto di chimica del riconoscimento molecolare (ICRM) (Istituto)
• Modellistica molecolare di proteine legate a processi patologici (PM.P01.026.002) (Modulo)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Human mutation (Rivista)

Insieme di parole chiave di

• Parole chiave di "A Gain-of-Glycosylation Mutation Associated with Myoclonus-Dystonia Syndrome Affects Trafficking and Processing of Mouse epsilon-Sarcoglycan in the Late Secretory Pathway" (Insieme di parole chiave)