title: A calcium signaling cascade essential for myosin thick filament assembly in Xenopus myocytes.
abstract: 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.
authors.affiliation: Department of Biology and Center for Molecular Genetics, University of California San Diego, La Jolla, California 92093-0357, USA. ferrari@biomail.ucsd.edu
authors.forename: M B
authors.initials: MB
authors.lastname: Ferrari
authors.forename: K
authors.initials: K
authors.lastname: Ribbeck
authors.forename: D J
authors.initials: DJ
authors.lastname: Hagler
authors.forename: N C
authors.initials: NC
authors.lastname: Spitzer
mesh_terms: 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
chemical_list: 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