Effects of an alpha-helical ryanodine receptor C-terminal tail peptide on ryanodine receptor activity: modulation by Homer




Pouliquin, Pierre
Pace, Suzy M
Curtis, Suzanne
Harvey, Peta
Gallant, Esther
Zorzato, Francesco
Casarotto, Marco
Dulhunty, Angela

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Pergamon-Elsevier Ltd


We have determined the structure of a domain peptide corresponding to the extreme 19 C-terminal residues of the ryanodine receptor Ca2+ release channel. We examined functional interactions between the peptide and the channel, in the absence and in the presence of the regulatory protein Homer. The peptide was partly α-helical and structurally homologous to the C-terminal end of the T1 domain of voltage-gated K+ channels. The peptide (0.1-10 μM) inhibited skeletal ryanodine receptor channels when the cytoplasmic Ca2+ concentration was 1 μM; but with 10 μM cytoplasmic Ca2+, skeletal ryanodine receptors were activated by ≤1.0 μM peptide and inhibited by 10 μM peptide. Cardiac ryanodine receptors on the other hand were inhibited by all peptide concentrations, at both Ca2+ concentrations. When channels did open in the presence of the peptide, they were more likely to open to substate levels. The inhibition and increased fraction of openings to subconductance levels suggested that the domain peptide might destabilise inter-domain interactions that involve the C-terminal tail. We found that Homer 1b not only interacts with the channels, but reduces the inhibitory action of the C-terminal tail peptide, perhaps by stabilizing inter-domain interactions and preventing their disruption.



Keywords: calcium ion; peptide; regulator protein; ryanodine receptor; voltage gated potassium channel; animal cell; article; calcium transport; carboxy terminal sequence; concentration (parameters); controlled study; cytoplasm; nonhuman; protein domain; protein fu C-terminal tail; Cardiac ryanodine receptor; Domain peptide; Homer adaptor proteins; Ryanodine receptor; Skeletal ryanodine receptor; Subconductance levels



The International Journal of Biochemistry and Cell Biology


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