A calcium signaling cascade essential for myosin thick filament assembly in Xenopus myocytes.
Spontaneous calcium release from intracellular stores occurs during myofibrillogenesis, the process of sarcomeric protein assembly in striated muscle. Preventing these Ca2+ transients disrupts sarcomere formation, but the signal transduction cascade has not been identified. Here we report that specific blockade of Ca2+ release from the ryanodine receptor (RyR) activated Ca2+ store blocks transients and disrupts myosin thick filament (A band) assembly. Inhibition of an embryonic Ca2+/calmodulin-dependent myosin light chain kinase (MLCK) by blocking the ATP-binding site, by allosteric phosphorylation, or by intracellular delivery of a pseudosubstrate peptide, also disrupts sarcomeric organization. The results indicate that both RyRs and MLCK, which have well-described calcium signaling roles in mature muscle contraction, have essential developmental roles during construction of the contractile apparatus.
Ferrari
M B
MB
Department of Biology and Center for Molecular Genetics, University of California San Diego, La Jolla, California 92093-0357, USA. ferrari@biomail.ucsd.edu
Ribbeck
K
K
Hagler
D J
DJ
Spitzer
N C
NC
D008841:Actin Cytoskeleton / Q000502:physiology*; D000818:Animals; D051943:Antennapedia Homeodomain Protein; D002118:Calcium / Q000378:metabolism*; D004789:Enzyme Activation; D018398:Homeodomain Proteins / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors*; D009218:Myosins / Q000378:metabolism*; D009687:Nuclear Proteins; D011493:Protein Kinase C / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors; D014982:Xenopus laevis
D051943:Antennapedia Homeodomain Protein; D018398:Homeodomain Proteins; D007527:Isoenzymes; D009687:Nuclear Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D014157:Transcription Factors; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase; D009218:Myosins; D002118:Calcium