RT Journal Article
T1 A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss.
A1 Servian-Morilla, Emilia
A1 Takeuchi, Hideyuki
A1 Lee, Tom V
A1 Clarimon, Jordi
A1 Mavillard, Fabiola
A1 Area-Gomez, Estela
A1 Rivas, Eloy
A1 Nieto-Gonzalez, Jose L
A1 Rivero, Maria C
A1 Cabrera-Serrano, Macarena
A1 Gomez-Sanchez, Leonardo
A1 Martinez-Lopez, Jose A
A1 Estrada, Beatriz
A1 Marquez, Celedonio
A1 Morgado, Yolanda
A1 Suarez-Calvet, Xavier
A1 Pita, Guillermo
A1 Bigot, Anne
A1 Gallardo, Eduard
A1 Fernandez-Chacon, Rafael
A1 Hirano, Michio
A1 Haltiwanger, Robert S
A1 Jafar-Nejad, Hamed
A1 Paradas, Carmen
K1 Notch
K1 O‐glycosylation
K1 POGLUT1
K1 muscular dystrophy
K1 satellite cell
AB Skeletal muscle regeneration by muscle satellite cells is a physiological mechanism activated upon muscle damage and regulated by Notch signaling. In a family with autosomal recessive limb-girdle muscular dystrophy, we identified a missense mutation in POGLUT1 (protein O-glucosyltransferase 1), an enzyme involved in Notch posttranslational modification and function. In vitro and in vivo experiments demonstrated that the mutation reduces O-glucosyltransferase activity on Notch and impairs muscle development. Muscles from patients revealed decreased Notch signaling, dramatic reduction in satellite cell pool and a muscle-specific α-dystroglycan hypoglycosylation not present in patients' fibroblasts. Primary myoblasts from patients showed slow proliferation, facilitated differentiation, and a decreased pool of quiescent PAX7+ cells. A robust rescue of the myogenesis was demonstrated by increasing Notch signaling. None of these alterations were found in muscles from secondary dystroglycanopathy patients. These data suggest that a key pathomechanism for this novel form of muscular dystrophy is Notch-dependent loss of satellite cells.
PB EMBO Press
YR 2016
FD 2016-11-02
LK http://hdl.handle.net/10668/10574
UL http://hdl.handle.net/10668/10574
LA en
NO Servián-Morilla E, Takeuchi H, Lee TV, Clarimon J, Mavillard F, Area-Gómez E, et al. A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss. EMBO Mol Med. 2016 Nov 2;8(11):1289-1309.
DS RISalud
RD Apr 11, 2025