FKRP-dependent glycosylation of fibronectin regulates muscle pathology in muscular dystrophy.
Nat Commun
; 12(1): 2951, 2021 05 19.
Article
en En
| MEDLINE
| ID: mdl-34012031
ABSTRACT
The muscular dystrophies encompass a broad range of pathologies with varied clinical outcomes. In the case of patients carrying defects in fukutin-related protein (FKRP), these diverse pathologies arise from mutations within the same gene. This is surprising as FKRP is a glycosyltransferase, whose only identified function is to transfer ribitol-5-phosphate to α-dystroglycan (α-DG). Although this modification is critical for extracellular matrix attachment, α-DG's glycosylation status relates poorly to disease severity, suggesting the existence of unidentified FKRP targets. Here we reveal that FKRP directs sialylation of fibronectin, a process essential for collagen recruitment to the muscle basement membrane. Thus, our results reveal that FKRP simultaneously regulates the two major muscle-ECM linkages essential for fibre survival, and establishes a new disease axis for the muscular dystrophies.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Pentosiltransferasa
/
Fibronectinas
/
Glicosiltransferasas
/
Proteínas de Pez Cebra
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Distrofias Musculares
/
Distrofia Muscular Animal
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Australia