title: Calcium Dyshomeostasis in Tubular Aggregate Myopathy.
abstract: 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 Ca2+in myofibers. Upon excitation, it releases Ca2+into the cytosol, inducing contraction of myofibrils. During relaxation, it takes up cytosolic Ca2+to terminate the contraction. During exercise, Ca2+is cycled between the cytosol and the SR through a system by which the Ca2+pool in the SR is restored by uptake of extracellular Ca2+via a specific channel on the plasma membrane. This channel is called the store-operated Ca2+channel or the Ca2+release-activated Ca2+channel. It is activated by depletion of the Ca2+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 Ca2+entry in calcium homeostasis. Finally, we discuss the phenotypes and the pathomechanism of myopathies caused by mutations in theSTIM1andORAI1genes.
authors.affiliation: Department of Genome Medicine Development, Medical Genome Center, National Center of Neurology and Neuropsychiatry, Kodaira, Tokyo 187-8551, Japan. azulmar@gmail.com.|Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Neuropsychiatry, Kodaira, Tokyo 187-8502, Japan. azulmar@gmail.com.
authors.forename: Jong-Mok
authors.initials: JM
authors.lastname: Lee
authors.affiliation: Department of Genome Medicine Development, Medical Genome Center, National Center of Neurology and Neuropsychiatry, Kodaira, Tokyo 187-8551, Japan. noguchi@ncnp.go.jp.|Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Neuropsychiatry, Kodaira, Tokyo 187-8502, Japan. noguchi@ncnp.go.jp.
authors.forename: Satoru
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002462:Cell Membrane / Q000378:metabolism; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D017136:Ion Transport; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D009210:Myofibrils / Q000378:metabolism / Q000473:pathology; D020914:Myopathies, Structural, Congenital / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D000071740:ORAI1 Protein / Q000235:genetics* / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002118:Calcium
keywords: ORAI1; SOCE; STIM1; calcium; severe combined immunodeficiency; skeletal muscle; tubular aggregate myopathy