Developmental and tissue-specific regulation of a novel dysferlin isoform.
Dysferlin plays an essential role in the muscle repair machinery, and its deficiency is associated with limb-girdle muscular dystrophy type 2B and with two different distal myopathies (Miyoshi myopathy and distal anterior compartment myopathy). Our aims were to characterize the pattern of dysferlin expression during myogenic cell differentiation and to assess possible differentially spliced isoforms of the DYSF gene. Human primary myogenic cells express a splice variant of dysferlin mRNA lacking exon 17 (Delta17), together with full-length dysferlin mRNA. Real-time polymerase chain reaction analysis of human myoblasts, myotubes, and normal skeletal muscle showed that Delta17 expression inversely correlates with muscle differentiation. Indeed, Delta17 is progressively replaced by the wild type as myoblast fusion proceeds, and it disappears in adult skeletal muscle. Conversely, Delta17 is the predominant dysferlin variant in mature peripheral nerve. Our findings suggest that the two proteins play different roles in myogenic cell differentiation and that dysferlin function in peripheral nerve might be accomplished by this novel isoform.
Salani
Sabrina
S
Centro Dino Ferrari, Dipartimento di Scienze Neurologiche, Università degli Studi di Milano, Istituti di Ricovero e Cura a Carattere Scientifico Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Lucchiari
Sabrina
S
Fortunato
Francesco
F
Crimi
Marco
M
Corti
Stefania
S
Locatelli
Federica
F
Bossolasco
Patrizia
P
Bresolin
Nereo
N
Comi
Giacomo Pietro
GP
D017398:Alternative Splicing; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D000073939:Dysferlin; D018507:Gene Expression Regulation, Developmental; D014644:Genetic Variation; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012584:Sciatic Nerve / Q000166:cytology / Q000378:metabolism*
C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger