Homer and the ryanodine receptor.

Homer proteins have recently been identified as novel high-affinity ligands that modulate ryanodine receptor (RyR) Ca(2+) release channels in heart and skeletal muscle, through an EVH1 domain which binds to proline-rich regions in target proteins. Many Homer proteins can also self-associate through a coiled-coil domain that allows their multimerisation. In other tissues, especially neurons, Homer anchors proteins embedded in the surface membrane to the Ca(2+) release channel in the endoplasmic reticulum and can anchor membrane or cytosolic proteins to the cytoskeleton.

Ca(2+) signaling in striated muscle: the elusive roles of triadin, junctin, and calsequestrin.

This review focuses on molecular interactions between calsequestrin, triadin, junctin and the ryanodine receptor in the lumen of the sarcoplasmic reticulum. These interactions modulate changes in Ca(2+) release in response to changes in the Ca(2+) load within the sarcoplasmic reticulum store in striated muscle and are of fundamental importance to Ca(2+) homeostasis, since massive adaptive changes occur when expression of the proteins is manipulated, while mutations in calsequestrin lead to functional changes which can be fatal. We find that calsequestrin plays a different role in the heart and skeletal muscle, enhancing Ca(2+) release in the heart, but depressing Ca(2+) release in skeletal muscle.

Ubiquitous SPRY domains and their role in the skeletal type ryanodine receptor.

We recently identified the second of three SPRY domains in the skeletal muscle ryanodine receptor type 1 (RyR1) as a potential binding partner in the RyR1 ion channel for the recombinant II-III loop of the skeletal muscle dihydropyridine receptor, for a scorpion toxin, Imperatoxin A and for an interdomain interaction within RyR1. SPRY domains are structural domains that were first described in the fungal Dictyostelium discoideum tyrosine kinase spore lysis A and all three isoforms of the mammalian ryanodine receptor (RyR). Our studies are the first to assign a function to any of the three SPRY domains in the RyR.