Homer Protein Increases Activation of Ca2+ Sparks in Permeabilized Skeletal Muscle

摘要: Members of the Homer family proteins are known to form multimeric complexes capable cross-linking plasma membrane channels (e.g. metabotropic glutamate receptor) and intracellular Ca2+ release inositol trisphosphate in neurons, which potentiates release. Recent work has demonstrated direct interaction with type 1 2 ryanodine receptor (RyR) isoforms. Moreover, have been shown modulate RyR-dependent isolated as well whole cell preparations. We now show that long short forms H1 (H1c H1-EVH1) potent activators via RyR skeletal muscle fibers sparks) modulators binding membranes enriched RyR, H1c being significantly more than H1-EVH1. did not alter spatio-temporal properties sparks, demonstrating increases rate opening RyRs, no change overall channel open time amount released during a spark. No changes spark frequency or were observed using full-length mutation EVH1 domain (H1c-G89N). One novel finding each agonist was combination their actions on [3H]ryanodine additive, an effect also for these agonists studies. Finally, studies, excess H1c-G89N prevented effects dominant negative manner. Taken together our results suggest is critical behavior sparks binding, coiled-coil domain, present but Homer, confers increase potential apparently through association ligand.