Int J Mol Sci. 2016 Nov 22;17(11). pii: E1952.
Calcium Dyshomeostasis in Tubular Aggregate Myopathy.
Calcium is a crucial mediator of cell signaling in skeletal muscles for basic cellular functions and specific functions, including contraction, fiber-type differentiation and energy production. The sarcoplasmic reticulum (SR) is an organelle that provides a large supply of intracellular Ca(2+) in myofibers. Upon excitation, it releases Ca(2+) into the cytosol, inducing contraction of myofibrils. During relaxation, it takes up cytosolic Ca(2+) to terminate the contraction. During exercise, Ca(2+) is cycled between the cytosol and the SR through a system by which the Ca(2+) pool in the SR is restored by uptake of extracellular Ca(2+) via a specific channel on the plasma membrane. This channel is called the store-operated Ca(2+) channel or the Ca(2+) release-activated Ca(2+) channel. It is activated by depletion of the Ca(2+) store in the SR by coordination of two main molecules: stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (ORAI1). Recently, myopathies with a dominant mutation in these genes have been reported and the pathogenic mechanism of such diseases have been proposed. This review overviews the calcium signaling in skeletal muscles and role of store-operated Ca(2+) entry in calcium homeostasis. Finally, we discuss the phenotypes and the pathomechanism of myopathies caused by mutations in the STIM1 and ORAI1 genes.
Tubular Aggregate Myopathyの臨床病理学的特徴について概説するとともに、その原因となる遺伝子変異、さらに変異から引き起こされる分子構造／機能変化について解説し、疾患の分子病態メカニズムを考察した。