title: Co-expression of MG29 and ryanodine receptor leads to apoptotic cell death: effect mediated by intracellular Ca2+ release.
abstract: Perturbation of intracellular Ca2+ homeostasis has been shown to regulate the process of cell proliferation and apoptosis. Our previous studies show that mitsugumin 29 (MG29), a synaptophysin-related protein localized in the triad junction of skeletal muscle, serves an essential role in muscle Ca2+ signaling by regulating the process of store-operated Ca2+ entry. Here we report a functional interaction between MG29 and the ryanodine receptor (RyR)/Ca2+ release channel. The purified MG29 protein enhances activity of the RyR/Ca2+ release channel incorporated into the lipid bilayer membrane. Co-expression of MG29 and RyR in Chinese hamster ovary cells leads to apoptotic cell death resulting from depletion of intracellular Ca2+ stores, despite neither protein expression alone exhibits any significant effect on cell viability. In transient expression studies, the presence of RyR in the endoplasmic reticulum leads to retention of MG29 from the plasma membrane into the intracellular organelles. This functional interaction between MG29 and RyR could have important implications in the Ca2+ signaling processes of muscle cells. Our data also show that perturbation of intracellular Ca2+ homeostasis can serve as a key signal in the initiation of apoptosis.
authors.affiliation: Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: Zui
authors.initials: Z
authors.lastname: Pan
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hirata
authors.forename: Ramakrishnan Y
authors.initials: RY
authors.lastname: Nagaraj
authors.forename: Jiying
authors.initials: J
authors.lastname: Zhao
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishi
authors.forename: Salim M
authors.initials: SM
authors.lastname: Hayek
authors.forename: Manjunatha B
authors.initials: MB
authors.lastname: Bhat
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
authors.forename: Jianjie
authors.initials: J
authors.lastname: Ma
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D004247:DNA / Q000737:chemistry; D004594:Electrophysiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel / Q000096:biosynthesis* / Q000502:physiology; D015398:Signal Transduction; D016708:Synaptophysin / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000502:physiology; D014162:Transfection
chemical_list: D008164:Luminescent Proteins; C491769:Mg29 protein, Oryctolagus cuniculus; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D016708:Synaptophysin; D049452:Green Fluorescent Proteins; D000255:Adenosine Triphosphate; D004247:DNA; D002118:Calcium