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Göteborgs universitets publikationer

ISPD produces CDP-ribitol used by FKTN and FKRP to transfer ribitol phosphate onto alpha-dystroglycan

Författare och institution:
I. Gerin (-); B. Ury (-); I. Breloy (-); C. Bouchet-Seraphin (-); J. Bolsee (-); M. Halbout (-); J. Graff (-); D. Vertommen (-); G. G. Muccioli (-); N. Seta (-); J. M. Cuisset (-); I. Dabaj (-); S. Quijano-Roy (-); Ammi Grahn (Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin); E. Van Schaftingen (-); G. T. Bommer (-)
Publicerad i:
Nature Communications, 7
ISSN:
2041-1723
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2016
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
Mutations in genes required for the glycosylation of alpha-dystroglycan lead to muscle and brain diseases known as dystroglycanopathies. However, the precise structure and biogenesis of the assembled glycan are not completely understood. Here we report that three enzymes mutated in dystroglycanopathies can collaborate to attach ribitol phosphate onto a-dystroglycan. Specifically, we demonstrate that isoprenoid synthase domain-containing protein (ISPD) synthesizes CDP-ribitol, present in muscle, and that both recombinant fukutin (FKTN) and fukutin-related protein (FKRP) can transfer a ribitol phosphate group from CDP-ribitol to alpha-dystroglycan. We also show that ISPD and FKTN are essential for the incorporation of ribitol into alpha-dystroglycan in HEK293 cells. Glycosylation of alpha-dystroglycan in fibroblasts from patients with hypomorphic ISPD mutations is reduced. We observe that in some cases glycosylation can be partially restored by addition of ribitol to the culture medium, suggesting that dietary supplementation with ribitol should be evaluated as a therapy for patients with ISPD mutations.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin
Nyckelord:
congenital muscular-dystrophy, walker-warburg syndrome, gram-positive, bacteria, fukutin-related protein, o-mannosylation, haemophilus-influenzae, mammalian-cells, posttranslational modification, streptococcus-pneumoniae, extracellular-matrix
Postens nummer:
240582
Posten skapad:
2016-08-22 14:20

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