Lack of Apobec2-related proteins causes a dystrophic muscle phenotype in zebrafish embryos.
The chaperones Unc45b and Hsp90a are essential for folding of myosin in organisms ranging from worms to humans. We show here that zebrafish Unc45b, but not Hsp90a, binds to the putative cytidine deaminase Apobec2 (Apo2) in an interaction that requires the Unc45/Cro1p/She4p-related (UCS) and central domains of Unc45b. Morpholino oligonucleotide-mediated knockdown of the two related proteins Apo2a and Apo2b causes a dystrophic phenotype in the zebrafish skeletal musculature and impairs heart function. These phenotypic traits are shared with mutants of unc45b, but not with hsp90a mutants. Apo2a and -2b act nonredundantly and bind to each other in vitro, which suggests a heteromeric functional complex. Our results demonstrate that Unc45b and Apo2 proteins act in a Hsp90a-independent pathway that is required for integrity of the myosepta and myofiber attachment. Because the only known function of Unc45b is that of a chaperone, Apo2 proteins may be clients of Unc45b but other yet unidentified processes cannot be excluded.
Etard
Christelle
C
Institute of Toxicology and Genetics, Forschungszentrum Karlsruhe in the Helmholtz Association, Karlsruhe Institute of Technology, Karlsruhe, Germany.
Roostalu
Urmas
U
Strähle
Uwe
U
D000818:Animals; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000196:embryology* / Q000378:metabolism; D010641:Phenotype; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D009124:Muscle Proteins; C472790:Unc45b protein, zebrafish; D029961:Zebrafish Proteins; D010738:Type C Phospholipases; C520787:plcb3 protein, zebrafish; D003564:Cytidine Deaminase