title: Restoration of Functional Glycosylation of α-Dystroglycan in FKRP Mutant Mice Is Associated with Muscle Regeneration.
abstract: Mutations in fukutin-related protein (FKRP) gene are characterized with lack of functionally glycosylated α-dystroglycan (F-α-DG). Surprisingly, a few muscle fibers express strong F-α-DG. Herein, we investigated the restoration of F-α-DG in the FKRP mutant muscles and showed that the restoration of glycosylation is associated with muscle regeneration and dependent on the expression of both like-glycosyltransferase (LARGE) and partially functional FKRP. F-α-DG in the regenerating fibers reaches up to normal levels and lasts for >4 weeks, but no up-regulation of the LARGE and FKRP is detected during the regeneration process. The FKRP protein with P448L mutation is sufficient for functional glycosylation of α-DG in regenerating fibers, but not in mature fibers. Thus, factors other than FKRP enable regenerating fibers to produce functional α-DG, compensating for the defect in FKRP function. Identification of factors other than LARGE and FKRP could generate new approaches for restoration of F-α-DG in mature muscle fibers with defects in FKRP functions.
authors.affiliation: McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research Center, Carolinas Medical Center, Charlotte, North Carolina.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Awano
authors.affiliation: McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research Center, Carolinas Medical Center, Charlotte, North Carolina.
authors.forename: Anthony
authors.initials: A
authors.lastname: Blaeser
authors.affiliation: McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research Center, Carolinas Medical Center, Charlotte, North Carolina.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Keramaris
authors.affiliation: McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research Center, Carolinas Medical Center, Charlotte, North Carolina.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research Center, Carolinas Medical Center, Charlotte, North Carolina.
authors.forename: Jason
authors.initials: J
authors.lastname: Tucker
authors.affiliation: McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research Center, Carolinas Medical Center, Charlotte, North Carolina.
authors.forename: Bo
authors.initials: B
authors.lastname: Wu
authors.affiliation: McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research Center, Carolinas Medical Center, Charlotte, North Carolina.
authors.forename: Pei
authors.initials: P
authors.lastname: Lu
authors.affiliation: McColl-Lockwood Laboratory for Muscular Dystrophy Research, Cannon Research Center, Carolinas Medical Center, Charlotte, North Carolina. Electronic address: qi.lu@carolinashealthcare.org.
authors.forename: Qi L
authors.initials: QL
authors.lastname: Lu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D049030:Dystroglycans / Q000378:metabolism*; D006031:Glycosylation; D016695:Glycosyltransferases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal; D018482:Muscle, Skeletal / Q000502:physiology*; D009136:Muscular Dystrophies; D020125:Mutation, Missense; D010430:Pentosyltransferases; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012038:Regeneration; D014166:Transferases
chemical_list: D011506:Proteins; D049030:Dystroglycans; D014166:Transferases; D016695:Glycosyltransferases; C499093:Fkrp protein, mouse; D010430:Pentosyltransferases