Department of Biological Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada.
Centre for Neuroscience, Brock University, St. Catharines, ON L2S 3A1, Canada.
Int J Mol Sci. 2020 Feb 4;21(3):1016. doi: 10.3390/ijms21031016.
Calmodulin (CaM) is an important Ca-sensing protein with numerous downstream targets that are either CaM-dependant or CaM-regulated. In muscle, CaM-dependent proteins, which are critical regulators of dynamic Ca handling and contractility, include calcineurin (CaN), CaM-dependant kinase II (CaMKII), ryanodine receptor (RyR), and dihydropyridine receptor (DHPR). CaM-regulated targets include genes associated with oxidative metabolism, muscle plasticity, and repair. Despite its importance in muscle, the regulation of CaM-particularly its availability to bind to and activate downstream targets-is an emerging area of research. In this minireview, we discuss recent studies revealing the importance of small IQ motif proteins that bind to CaM to either facilitate (nuclear receptor interacting protein; NRIP) its activation of downstream targets, or sequester (neurogranin, Ng; and growth-associated protein 43, GAP43) CaM away from their downstream targets. Specifically, we discuss recent studies that have begun uncovering the physiological roles of NRIP, Ng, and GAP43 in skeletal and cardiac muscle, thereby highlighting the importance of endogenously expressed CaM-binding proteins and their regulation of CaM in muscle.
钙调蛋白（CaM）是一种重要的钙感应蛋白，具有许多下游靶标，这些靶标要么依赖 CaM，要么受 CaM 调节。在肌肉中，钙调蛋白依赖性蛋白是动态钙处理和收缩性的关键调节剂，包括钙调磷酸酶（CaN）、钙调蛋白依赖性激酶 II（CaMKII）、兰尼碱受体（RyR）和二氢吡啶受体（DHPR）。CaM 调节的靶标包括与氧化代谢、肌肉可塑性和修复相关的基因。尽管 CaM 在肌肉中非常重要，但 CaM 的调节，特别是其与下游靶标结合并激活下游靶标的能力，是一个新兴的研究领域。在这篇综述中，我们讨论了最近的研究揭示了与 CaM 结合的小 IQ motif 蛋白的重要性，这些蛋白要么促进（核受体相互作用蛋白；NRIP）其对下游靶标的激活，要么将 CaM （神经颗粒蛋白，Ng；和生长相关蛋白 43，GAP43）从其下游靶标上隔离。具体来说，我们讨论了最近的研究开始揭示 NRIP、Ng 和 GAP43 在骨骼肌和心肌中的生理作用，从而强调了内源性表达的 CaM 结合蛋白及其对肌肉中 CaM 的调节的重要性。
