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dc.contributor.authorAlhamidi, Maisoon
dc.contributor.authorKjeldsen, Elisabeth
dc.contributor.authorFagerheim, Toril
dc.contributor.authorBrox, Vigdis
dc.contributor.authorLindal, Sigurd
dc.contributor.authorVan Ghelue, Marijke
dc.contributor.authorNilssen, Øivind
dc.date.accessioned2012-03-14T14:35:12Z
dc.date.available2012-03-14T14:35:12Z
dc.date.issued2011
dc.description.abstractLimb-Girdle Muscular Dystrophy type 2I (LGMD2I) is an inheritable autosomal, recessive disorder caused by mutations in the FuKutin-Related Protein (FKRP) gene (FKRP) located on chromosome 19 (19q13.3). Mutations in FKRP are also associated with Congenital Muscular Dystrophy (MDC1C), Walker-Warburg Syndrome (WWS) and Muscle Eye Brain disease (MEB). These four disorders share in common an incomplete/aberrant O-glycosylation of the membrane/extracellular matrix (ECM) protein a-dystroglycan. However, further knowledge on the FKRP structure and biological function is lacking, and its intracellular location is controversial. Based on immunogold electron microscopy of human skeletal muscle sections we demonstrate that FKRP co-localises with the middle-to-trans-Golgi marker MG160, between the myofibrils in human rectus femoris muscle fibres. Chemical cross-linking experiments followed by pairwise yeast 2-hybrid experiments, and co-immune precipitation, demonstrate that FKRP can exist as homodimers as well as in large multimeric protein complexes when expressed in cell culture. The FKRP homodimer is kept together by a disulfide bridge provided by the most N-terminal cysteine, Cys6. FKRP contains N-glycan of high mannose and/or hybrid type; however, FKRP N-glycosylation is not required for FKRP homodimer or multimer formation. We propose a model for FKRP which is consistent with that of a Golgi resident type II transmembrane protein.en
dc.identifier.citationPLoS ONE (2011) 6(8): e22968en
dc.identifier.cristinIDFRIDAID 848346
dc.identifier.doidoi: 10.1371/journal.pone.0022968
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/10037/3969
dc.identifier.urnURN:NBN:no-uit_munin_3691
dc.language.isoengen
dc.publisherPublic Library of Science (PLoS)en
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714en
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714en
dc.titleFukutin-Related Protein Resides in the Golgi Cisternae of Skeletal Muscle Fibres and Forms Disulfide-Linked Homodimers via an N-Terminal Interactionen
dc.typeJournal articleen
dc.typeTidsskriftartikkelen
dc.typePeer revieweden


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