Regulation of RYR1 Activity by Ca2+ and Calmodulin

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• 作者：George G. Rodney ; Barbara Y. Williams ; Gale M. Strasburg ; Kathy Beckingham ; and Susan L. Hamilton
• 刊名：Biochemistry
• 出版年：2000
• 出版时间：July 3, 2000
• 年：2000
• 卷：39
• 期：26
• 页码：7807 - 7812
• 全文大小：110K
• 年卷期：v.39,no.26(July 3, 2000)
• ISSN：1520-4995

文摘

The skeletal muscle calcium release channel (RYR1) is a Ca²⁺-binding protein that is regulatedby another Ca²⁺-binding protein, calmodulin. The functional consequences of calmodulin's interactionwith RYR1 are dependent on Ca²⁺ concentration. At nanomolar Ca²⁺ concentrations, calmodulin is anactivator, but at micromolar Ca²⁺ concentrations, calmodulin is an inhibitor of RYR1. This raises thequestion of whether the Ca²⁺-dependent effects of calmodulin on RYR1 function are due to Ca²⁺ bindingto calmodulin, RYR1, or both. To distinguish the effects of Ca²⁺ binding to calmodulin from those ofCa²⁺ binding to RYR1, a mutant calmodulin that cannot bind Ca²⁺ was used to evaluate the effects ofCa²⁺-free calmodulin on Ca²⁺-bound RYR1. We demonstrate that Ca²⁺-free calmodulin enhances theaffinity of RYR1 for Ca²⁺ while Ca²⁺ binding to calmodulin converts calmodulin from an activator to aninhibitor. Furthermore, Ca²⁺ binding to RYR1 enhances its affinity for both Ca²⁺-free and Ca²⁺-boundcalmodulin.