Ablation of Cypher, a PDZ-LIM domain Z-line protein, causes a severe form of congenital myopathy.
Cypher is a member of a recently emerging family of proteins containing a PDZ domain at their NH(2) terminus and one or three LIM domains at their COOH terminus. Cypher knockout mice display a severe form of congenital myopathy and die postnatally from functional failure in multiple striated muscles. Examination of striated muscle from the mutants revealed that Cypher is not required for sarcomerogenesis or Z-line assembly, but rather is required for maintenance of the Z-line during muscle function. In vitro studies demonstrated that individual domains within Cypher localize independently to the Z-line via interactions with alpha-actinin or other Z-line components. These results suggest that Cypher functions as a linker-strut to maintain cytoskeletal structure during contraction.
Zhou
Q
Q
Institute of Molecular Medicine and Department of Medicine, University of California at San Diego School of Medicine, La Jolla, CA 92093, USA.
Chu
P H
PH
Huang
C
C
Cheng
C F
CF
Martone
M E
ME
Knoll
G
G
Shelton
G D
GD
Evans
S
S
Chen
J
J
D000185:Actinin / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins; D002478:Cells, Cultured; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000473:pathology; D009206:Myocardium / Q000166:cytology; D020914:Myopathies, Structural, Congenital / Q000378:metabolism*; D051381:Rats
C498529:Actn2 protein, mouse; C498530:Actn2 protein, rat; D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; D002352:Carrier Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; C485639:Ldb3 protein, mouse; D009124:Muscle Proteins; D000185:Actinin