title: A combinatorial role for NFAT5 in both myoblast migration and differentiation during skeletal muscle myogenesis.
abstract: Skeletal muscle regeneration depends on myoblast migration, differentiation and myofiber formation. Isoforms of the nuclear factor of activated T cells (NFAT) family of transcription factors display nonredundant roles in skeletal muscle. NFAT5, a new isoform of NFAT, displays many differences from NFATc1-c4. Here, we examine the role of NFAT5 in myogenesis. NFAT5+/- mice displayed a defect in muscle regeneration with fewer myofibers formed at early times after injury. NFAT5 has a muscle-intrinsic function because inhibition of NFAT5 transcriptional activity caused both a migratory and differentiation defect in cultured myoblasts. We identified Cyr61 as a target of NFAT5 signaling in skeletal muscle cells. Addition of Cyr61 to cells expressing inhibitory forms of NFAT5 rescued the migratory phenotype. These results demonstrate a role for NFAT5 in skeletal muscle cell migration and differentiation. Furthermore, as cell-cell interactions are crucial for myoblast differentiation, these data suggest that myoblast migration and differentiation are coupled and that NFAT5 is a key regulator.
authors.affiliation: Graduate Program in Molecular and Systems Pharmacology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Roddy S
authors.initials: RS
authors.lastname: O'Connor
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Mills
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Jones
authors.forename: Steffan N
authors.initials: SN
authors.lastname: Ho
authors.forename: Grace K
authors.initials: GK
authors.lastname: Pavlath
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology; D032446:Myoblasts / Q000166:cytology* / Q000502:physiology*; D009210:Myofibrils / Q000502:physiology; D010641:Phenotype; D012038:Regeneration / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: C491850:CCN1 protein, mouse; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; C492200:Nfat5 protein, mouse; D014157:Transcription Factors