Truncated CASK does not alter skeletal muscle or protein interactors.
CASK (Ca2+, calmodulin-associated serine/threonine kinase) is an essential mammalian cell junction protein and is also crucial at Drosophila neuromuscular synapses. We have shown that CASK is present in mammalian skeletal muscle at the postsynaptic membrane of the neuromuscular junction. CASK interacts biochemically with channels at central synapses, and studies in cultured cells have led to proposed functions for CASK. However, in vivo functions of CASK in skeletal muscle remain unknown. To test hypotheses of CASK functions, we generated two lines of transgenic mice, which overexpress full-length and truncated CASK protein in skeletal muscle. Extensive analyses showed that overexpression of CASK protein did not affect the morphology or physiology of skeletal muscle, the morphology of the neuromuscular junction, or the levels or distribution of protein interactors. These results contrast with previous cell culture experiments and emphasize the importance of in vivo analysis of protein function.
Sanford
Jamie L
JL
Department of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, 410 Hamilton Hall, 1645 Neil Avenue, Columbus, Ohio 43210, USA.
Mays
Tessily A
TA
Varian
Kenneth D
KD
Wilson
Joanna B
JB
Janssen
Paul M L
PM
Rafael-Fortney
Jill A
JA
D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002038:Bungarotoxins / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation / Q000235:genetics*; D051528:Guanylate Kinases / Q000235:genetics* / Q000378:metabolism*; D018737:Hand Strength / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics*; D009469:Neuromuscular Junction / Q000378:metabolism / Q000648:ultrastructure; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014162:Transfection
D002038:Bungarotoxins; C489463:Kir2.2 channel; C120997:NR2A NMDA receptor; D024661:Potassium Channels, Inwardly Rectifying; D016194:Receptors, N-Methyl-D-Aspartate; C106868:CASK kinases; D051528:Guanylate Kinases