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• W2040595410 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. 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. Ca2+ as a second messenger plays important roles in a variety of cellular processes, ranging from cell motility to enzymatic control, and to gene regulation and apoptosis. The ryanodine receptors (RyR) 1The abbreviations used are: RyR, ryanodine receptor; MG29, mitsugumin 29; ER, endoplasmic reticulum; GFP, green fluorescent protein; CHO, Chinese hamster ovary; mAb, monoclonal antibody; pAb, polyclonal antibody; CHAPS, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid; IP3, inositol 1,4,5-trisphosphate. 1The abbreviations used are: RyR, ryanodine receptor; MG29, mitsugumin 29; ER, endoplasmic reticulum; GFP, green fluorescent protein; CHO, Chinese hamster ovary; mAb, monoclonal antibody; pAb, polyclonal antibody; CHAPS, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid; IP3, inositol 1,4,5-trisphosphate./Ca2+ release channels are present in the endo/(sarco)plasmic reticulum of virtually every cell types, providing a pathway for fast Ca2+ release from intracellular stores (1Takeshima H. Nishimura S. Matsumoto T. Ishida H. Kangawa K. Minamino N. Matsuo H. Ueda M. Hanaoka M. Hirose T. Numa S. Nature. 1989; 339: 439-445Crossref PubMed Scopus (856) Google Scholar, 2Fill M. Copello J.A. Physiol. Rev. 2002; 82: 893-922Crossref PubMed Scopus (867) Google Scholar, 3McPherson P.S. Campbell K.P. J. Biol. Chem. 1993; 268: 13765-13768Abstract Full Text PDF PubMed Google Scholar, 4Sutko J.L. Airey J.A. Physiol. Rev. 1996; 76: 1027-1071Crossref PubMed Scopus (363) Google Scholar). Mitsugumin29 (MG29) is a novel membrane protein localized specifically to the triad junction of skeletal muscle (5Takeshima H. Shimuta M. Komazaki S. Ohmi K. Nishi M. Iino M. Miyata A. Kangawa K. Biochem. J. 1998; 331: 317-322Crossref PubMed Scopus (82) Google Scholar). The primary amino acid sequence of MG29 shares ∼45% homology to synaptophysin, a family of proteins with presumed roles in secretion and neurotransmitter release (6Johnston P.A. Jahn R. Sudhof T.C. J. Biol. Chem. 1989; 264: 1265-1273Google Scholar, 7Alder J. Lu B. Valtorta F. Greengard P. Poo M. Science. 1992; 257: 657-661Crossref PubMed Scopus (126) Google Scholar). The MG29 protein appears to participate in the excitation-contraction coupling process of skeletal muscle, since mutant mice lacking the MG29 gene exhibit apparent reduction in contractile force, with altered structure of the triad junction (8Nishi M. Komazaki S. Kurebayashi N. Ogawa Y. Noda T. Iino M. Takeshima H. J. Cell Biol. 1999; 147: 1473-1480Crossref PubMed Scopus (72) Google Scholar), and increased susceptibility to fatigue of the skeletal muscle (9Pan Z. Yang D. Nagaraj R.Y. Nosek T.A. Nishi M. Takeshima H. Cheng H. Ma J. Nat. Cell Biol. 2002; 4: 379-383Crossref PubMed Scopus (145) Google Scholar, 10Nagaraj R.Y. Nosek C.M. Brotto M.A. Nishi M. Takeshima H. Nosek T.M. Ma J. Physiol. Genomics. 2000; 4: 43-49Crossref PubMed Google Scholar). Several studies have suggested a central role for the participation of endoplasmic reticulum (ER) and intracellular Ca2+ release in the initiation of apoptosis (11Breckenridge D.G. Germain M. Mathai J.P. Nguyen M. Shore G.C. Oncogene. 2003; 22: 8608-8618Crossref PubMed Scopus (643) Google Scholar, 12Hajnoczky G. Davies E. Madesh M. Biochem. Biophys. Res. Commun. 2003; 304: 445-454Crossref PubMed Scopus (387) Google Scholar, 13Ferrari D. Pinton P. Szabadkai G. Chami M. Campanella M. Pozzan T. Rizzuto R. Cell Calcium. 2002; 32: 413-420Crossref PubMed Scopus (97) Google Scholar). Our previous studies have shown that depletion of intracellular Ca2+ stores via activation of the RyR/Ca2+ release channel could induce apoptosis (14Pan Z. Damron D. Nieminen A.L. Bhat M.B. Ma J. J. Biol. Chem. 2000; 275: 19978-19984Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar, 15Pan Z. Bhat M.B. Nieminen A.L. Ma J. J. Biol. Chem. 2001; 276: 32257-32263Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar). Here we tested the hypothesis that overexpression of MG29 can influence the intracellular Ca2+ homeostasis through changes of the RyR/Ca2+ release function. We show that co-expression of MG29 and RyR in cultured cells leads to apoptotic cell death resulting from depletion of intracellular Ca2+ stores, and the purified MG29 protein can enhance activity of the RyR/Ca2+ release channel incorporated into the lipid bilayer membrane. Our data provide evidence for a functional interaction between the RyR and MG29 proteins, which adds insights into the function of MG29 in excitation-contraction coupling of muscle cells, and the cellular mechanism of Ca2+ signaling in apoptosis. Cloning and Mutagenesis—The cDNA encoding the green fluorescent protein (GFP) was ligated to the 5′ end of the MG29 cDNA (5Takeshima H. Shimuta M. Komazaki S. Ohmi K. Nishi M. Iino M. Miyata A. Kangawa K. Biochem. J. 1998; 331: 317-322Crossref PubMed Scopus (82) Google Scholar) and cloned into the pcDNA3 vector (Invitrogen) to yield the GFP-MG29 fusion construct. The GFP-RyR construct was obtained by replacing the first 290 amino acids of the rabbit skeletal muscle RyR with GFP (16Bhat M.B. Zhao J. Zang W. Balke C.W. Takeshima H. Wier W.G. Ma J. J. Gen. Physiol. 1997; 110: 749-762Crossref PubMed Scopus (83) Google Scholar). The E4032A RyR mutant was generated using site-directed mutagenesis, as described in previous studies (14Pan Z. Damron D. Nieminen A.L. Bhat M.B. Ma J. J. Biol. Chem. 2000; 275: 19978-19984Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar). Cell Culture, Transfection, and DNA Laddering—c1148 and mg-5 are stable clones of Chinese hamster ovary (CHO) cells permanently expressing the RyR and MG29 proteins, respectively. The cells were grown at 37 °C and 5% CO2 in Ham's F-12 medium supplemented with 10% fetal bovine serum, 100 units/ml penicillin, 100 μg/ml streptomycin, and 0.5 mg/ml G418. Transfections of GFP-MG29 into c1148 cells and GFP-RyR into mg-5 cells were mediated by the LipofectAMINE reagent (15Pan Z. Bhat M.B. Nieminen A.L. Ma J. J. Biol. Chem. 2001; 276: 32257-32263Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar, 16Bhat M.B. Zhao J. Zang W. Balke C.W. Takeshima H. Wier W.G. Ma J. J. Gen. Physiol. 1997; 110: 749-762Crossref PubMed Scopus (83) Google Scholar, 17Bhat M.B. Zhao J. Takeshima H. Ma J. Biophys. J. 1997; 73: 1329-1336Abstract Full Text PDF PubMed Scopus (115) Google Scholar). Genomic DNA were collected from CHO cells transfected with various plasmids, and electrophoresis was performed (14Pan Z. Damron D. Nieminen A.L. Bhat M.B. Ma J. J. Biol. Chem. 2000; 275: 19978-19984Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar). Confocal Microscopy—For subcellular localization of GFP-MG29 and GFP-RyR transiently expressed in CHO cells, the cells were grown on glass-bottomed microwell dishes and visualized with a Bio-Rad Radiance 2100 or Zeiss LSM510 laser scanning confocal microscope (18Heiskanen K.M. Bhat M.B. Wang H.-W. Ma J. Nieminen A.-L. J. Biol. Chem. 1999; 274: 5654-5658Abstract Full Text Full Text PDF PubMed Scopus (305) Google Scholar). For immunolocalization of RyR stably expressed in the c1148 cells or caveolin in CHO cells, the cells were first treated with antibody against RyR (mAb 34C) or caveolin-1 (pAb C3237, Sigma) and then labeled with an appropriate secondary antibody conjugated with Texas Red. To monitor the cell death process, 10 μm Hoechst 33342 (Molecular Probes) was added to the culture medium for 10 min at 37 °C (14Pan Z. Damron D. Nieminen A.L. Bhat M.B. Ma J. J. Biol. Chem. 2000; 275: 19978-19984Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar). Separate filter sets for GFP (488 nm excitation, a 500–550 nm band pass emission), Texas Red (543 nm excitation, 560 nm long pass emission), and Hoechst (351 nm excitation, 385–470 emission) were used for image acquisitions. Intracellular Ca2+ Measurement—The different clones of CHO cells (parental, c1148, mg-5; and after transient transfection with GFP-MG29 or GFP-RyR) were loaded with 2 μm Fura 2-AM for 30 min at 37 °C, in a balanced salt solution (14Pan Z. Damron D. Nieminen A.L. Bhat M.B. Ma J. J. Biol. Chem. 2000; 275: 19978-19984Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar). The release of intracellular Ca2+ in individual cells was measured following exposure to either caffeine or ATP in a Ca2+-free solution by rapid solution exchange. Due to the apoptosis process, the Ca2+ measurements with c1148 cells transfected with GFP-MG29 or mg-5 cells transfected with GFP-RyR were performed 14–17 h after transfection. GFP fluorescence was used to select for transfected cells that are in the pre-apoptotic stage. Vesicle Isolation and Protein Purification—Microsomal membrane vesicles containing MG29 or RyR proteins were isolated from the mg-5 or c1148 cells following the procedure of Bhat et al. (17Bhat M.B. Zhao J. Takeshima H. Ma J. Biophys. J. 1997; 73: 1329-1336Abstract Full Text PDF PubMed Scopus (115) Google Scholar). For purification of the MG29 proteins, the vesicles were solubilized with 1% CHAPS in a buffer containing 0.5 m NaCl, 0.5 m sucrose, 20 mm Tris-HCl (pH 7.4). The solubilized proteins were loaded onto a CNBr-activated Sepharose column that had the anti-MG29 antibody (mAb 1007) bound to it. The column was washed, and the MG29 protein was eluted with 0.3% CHAPS, 0.5 m NaSCN, 20 mm Tris-Cl (pH 7.4). The NaSCN was removed from the final buffer through dilution dialysis. Electrophysiology—Lipid bilayer membranes were formed with a mixture of phosphatidylserine:phosphatidylethanolamine:cholesterol (6:6:1). Incorporation of the Ca2+-release channel in bilayers was achieved by addition of microsomal membrane vesicles isolated from the c1148 cells to the cis solution, under a concentration gradient of 200 mm (cis)/50 mm (trans) cesium gluconate (17Bhat M.B. Zhao J. Takeshima H. Ma J. Biophys. J. 1997; 73: 1329-1336Abstract Full Text PDF PubMed Scopus (115) Google Scholar). The purified MG29 was added to the cis solution to study the interaction with the Ca2+-release channel. Using monoclonal antibodies against triad junctional proteins from rabbit skeletal muscle, we have identified MG29, a membrane protein specifically localized to the triad junction of skeletal muscle. The primary structure deduced by cDNA cloning revealed that MG29 is a novel member of the synaptophysin family, with ∼45% identity in amino acid sequence to synaptophysin (5Takeshima H. Shimuta M. Komazaki S. Ohmi K. Nishi M. Iino M. Miyata A. Kangawa K. Biochem. J. 1998; 331: 317-322Crossref PubMed Scopus (82) Google Scholar). The cDNAs encoding either MG29 or RyR from rabbit skeletal muscle were introduced into the CHO cells using the Ca2+-phosphate precipitation method (19Takekura H. Takeshima H. Nishimura S. Takahashi M. Tanabe T. Flockerzi V. Hofmann F. Franzini-Armstrong C. J. Muscle Res. Cell Motil. 1995; 16: 465-480Crossref PubMed Scopus (50) Google Scholar). Following selection with G418, individual clones of CHO cells stably expressing either MG29 (mg-5) or RyR (c1148) were selected (Fig. 1a). The levels of protein expression in these cells were maintained in multiple passages, suggesting that the CHO cells can take up well these exogenous MG29 or RyR proteins. For subcellular localization of MG29 expressed in CHO cells, GFP-MG29 fusion construct was generated. Confocal microscopic images indicate that GFP-MG29 can be clearly visualized at the cell surface membrane in a punctuated fashion 2 days after transfection (Fig. 1b). A similar punctated-vesicular labeling of MG29 was also observed in mg-5 cells, with a monoclonal antibody against MG29 (mAb 1007; data not shown). In co-localization studies, a certain degree of overlap in the membrane distribution of MG29 and caveolin-1, an endogenous caveolae-specific protein present in CHO cells, could be observed in CHO cells (Fig. 1b). Such characteristic patterns of MG29 expression in CHO cells suggest that as yet unknown cellular mechanisms probably result in concentration of MG29 at certain subdomains of the plasma membrane (e.g. rafts or caveolae). These data are also consistent with the specific localization of MG29 at the transverse-tubule membrane of matured skeletal muscle cells (20Komazaki S. Nishi M. Kangawa K. Takeshima H. Dev. Dyn. 1999; 215: 87-95Crossref PubMed Scopus (21) Google Scholar). Interestingly, transient expression of GFP-MG29 in c1148 cells revealed a different pattern of fluorescence distribution (Fig. 1c). The c1148 cells are bigger than the parental CHO cells, as has been reported in our previous studies (16Bhat M.B. Zhao J. Zang W. Balke C.W. Takeshima H. Wier W.G. Ma J. J. Gen. Physiol. 1997; 110: 749-762Crossref PubMed Scopus (83) Google Scholar). It appears that the presence of RyR in the ER membrane facilitates the retention of GFP-MG29 to the perinuclear regions and also causes apparent aggregation of GFP-MG29 (Fig. 1c). The distribution of caveolin-1 in c1148 cells, however, did not appear to be different from that of the parental CHO cells (Fig. 1d) This result suggests that the presence of RyR in the ER membrane likely alter the trafficking or processing properties of MG29. To test the potential interaction between RyR and MG29, we used co-expression in CHO cells. However, multiple attempts to generate stable clones of CHO cells co-expressing MG29 and RyR failed, because the cells always underwent apoptosis after co-transfection. This apoptotic process occurred either when the MG29 cDNA was introduced into the c1148 cells (n = 7) or when the RyR cDNA was introduced into the mg-5 cells (n = 6). Transient expression of GFP-MG29 in c1148 cells and GFP-RyR in mg-5 cells were therefore used to monitor the cell death process. To differentiate apoptosis from necrosis, the cells were loaded with a Hoechst 33342 dye, which labeled the nuclear chromatin of a cell undergoing apoptosis (14Pan Z. Damron D. Nieminen A.L. Bhat M.B. Ma J. J. Biol. Chem. 2000; 275: 19978-19984Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar). As shown in Fig. 2a, expression of GFP-MG29 in c1148 cells could be observed within 12 h after transfection, at which time most of the cells appear to be healthy. By 36 h, a lot of the cells started to die as revealed by the blebbing of the plasma membrane, diffused distribution of GFP fluorescence, and fragmented staining of the nucleus by the Hoechst dye. By 72 h, nearly all the transfected cells were dead. A similar pattern of cell death process was also observed with the mg-5 cells transfected with GFP-RyR (not shown, n = 6). Moreover, electrophoresis of genomic DNA isolated from c1148 cells transfected with MG29 revealed characteristic pattern of DNA laddering, a hallmark of cells undergoing apoptosis (Fig. 2b). In contrast, the parental CHO cells and those cells stably expressing the E4032A mutant of RyR did not exhibit apparent DNA laddering following identical treatment with the MG29 cDNA (Fig. 2b). Since the E4032A RyR mutant is know to have defective Ca2+ release channel function (21Xiao B. Masumiya H. Jiang D. Wang R. Sei Y. Zhang L. Murayama T. Ogawa Y. Lai F.A. Wagenknecht T. Chen S.R. J. Biol. Chem. 2002; 277: 41778-41785Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar), and we have shown that stable expression of E4032A did not affect the proliferation and apoptosis of CHO cells (14Pan Z. Damron D. Nieminen A.L. Bhat M.B. Ma J. J. Biol. Chem. 2000; 275: 19978-19984Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar), the MG29 overexpression-induced apoptosis of c1148 cells is probably related to the RyR-mediated Ca2+ release from the ER membrane. Further studies show that co-expression of MG29 and RyR in the ER membrane leads to drastic changes in the intracellular Ca2+ homeostasis in CHO cells (Fig. 3). The release of Ca2+ from the ER membrane was measured in individual CHO cells following stimulation with 10 mm caffeine or 200 μm ATP. Caffeine is a known activator of the RyR/Ca2+ release channel, and ATP is an agonist of the purinergic receptor on the plasma membrane, which activates the IP3 receptor on the ER membrane via generation of IP3 (22Iredale P.A. Hill S.J. Br. J. Pharmacol. 1993; 110: 1305-1310Crossref PubMed Scopus (106) Google Scholar). As shown in Fig. 3a, the parental CHO cells do not respond to caffeine but contain active IP3 receptors as indicated by the rapid release of Ca2+ triggered by ATP (n = 30). Both caffeine and ATP caused rapid release of intracellular Ca2+ in the c1148 cells (Fig. 3b, n = 66/67). Expression of MG29 in CHO cells alone did not affect the ER Ca2+ pool, since the response of mg-5 cells to ATP was similar to the parental CHO cells (Fig. 3c, n = 8). 14–17 h after transfection of GFP-MG29 into c1148 cells, the amount of Ca2+ in the ER was diminished, since the cells showed significantly reduced responses to either caffeine or ATP (Fig. 3e). This was likely due to the activation of RyR, because CHO cells stably transfected with the E4032A mutant did not show changes of their ER Ca2+ store upon introduction of GFP-MG29 (Fig. 3d). Similarly, expression of GFP-RyR in mg-5 cells also resulted in reduction of the ER Ca2+ pool (Fig. 3f). The traces shown in Fig. 3, e and f, were representative of 13/17 and 8/9 experiments performed, i.e. over 75% of the transfected cells had an ER Ca2+ content that was nearly empty. These fluorescent cells, expressing both GFP-MG29 and RyR or both GFP-RyR and MG29, generally died within 24–36 h after transfection. On the other hand, non-transformed cells expressing either RyR or MG29 showed intact ER Ca2+ pools and remained viable. Thus it appears that there is a close correlation between cellular apoptosis and Ca2+ homeostasis, which has been observed in our previous studies (14Pan Z. Damron D. Nieminen A.L. Bhat M.B. Ma J. J. Biol. Chem. 2000; 275: 19978-19984Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar). It is possible that the interaction between RyR and MG29 enhances the activity of the Ca2+ release channel or alters the trafficking and function of MG29, which leads to the depletion of Ca2+ from the ER membrane. We next purified the MG29 protein from the mg-5 cells and tested its effect on the individual RyR/Ca2+ release channel using the lipid bilayer reconstitution system (Fig. 4). Microsomal membrane vesicles were isolated from mg-5 cells and solubilized with the CHAPS detergent, from which the MG29 protein was purified to homogeneity using a monoclonal antibody affinity column (Fig. 4a). A single RyR/Ca2+ release channel was incorporated into the lipid bilayer by fusing vesicles isolated from the c1148 cells (Fig. 4b). The RyR channel had an ohmic conductance of ∼400 picosiemens, which exhibited fast transitions between the open and closed states (16Bhat M.B. Zhao J. Zang W. Balke C.W. Takeshima H. Wier W.G. Ma J. J. Gen. Physiol. 1997; 110: 749-762Crossref PubMed Scopus (83) Google Scholar). At a test potential of –50 mV with free [Ca2+] buffered at 220 μm and 5 mm MgCl2 added to the cytosolic solution, the channel had an average open probability of Po = 0.007 ± 0.002 (n = 4). Following addition of the purified MG29 protein (0.05–0.2 μg/ml) to the cytosolic solution, open probability of the Ca2+ release channel was increased significantly (Po = 0.052 ± 0.006, n = 4, p < 0.001), whereas the single channel current amplitude remained unchanged (Fig. 4c). This result supports a direct functional interaction between MG29 and RyR. Taken together, our data show that a functional interaction between MG29 and RyR in CHO cells enhances opening of the Ca2+ release channel, which likely causes depletion of the intracellular Ca2+ pool, leading the cells to undergo apoptosis. We also showed that the presence of RyR in the ER membrane could influence the processing and trafficking properties of MG29, causing retention of MG29 from plasma membrane to the intracellular organelles. This result is interesting but not surprising. We know that MG29 exists as an oligomer in the transverse-tubule membrane of matured skeletal muscle (23Brandt N.R. Caswell A.H. Arch. Biochem. Biophys. 1999; 371: 348-350Crossref PubMed Scopus (12) Google Scholar). We also know that a significant portion of MG29 co-localize with the SR membrane in the developing skeletal muscle (20Komazaki S. Nishi M. Kangawa K. Takeshima H. Dev. Dyn. 1999; 215: 87-95Crossref PubMed Scopus (21) Google Scholar). In addition, knock-out of MG29 has been shown to cause fragmentation of the SR membrane (8Nishi M. Komazaki S. Kurebayashi N. Ogawa Y. Noda T. Iino M. Takeshima H. J. Cell Biol. 1999; 147: 1473-1480Crossref PubMed Scopus (72) Google Scholar). Thus, there appears to be a close association between the expression pattern of MG29 and the ultrastructure of the membrane cross-talk in skeletal muscle. Perhaps, a functional interaction between MG29 and RyR could have a significant role in the overall Ca2+ signaling process in muscle cells, at least in the regulation of store-operated Ca2+ entry (9Pan Z. Yang D. Nagaraj R.Y. Nosek T.A. Nishi M. Takeshima H. Cheng H. Ma J. Nat. Cell Biol. 2002; 4: 379-383Crossref PubMed Scopus (145) Google Scholar). It is interesting that although both MG29 and RyR are essential for the normal contractile function of the skeletal muscle, co-expression or overexpression of MG29 and RyR in CHO cells leads to eventual cell death due to the leakage of the ER Ca2+ store. Therefore, to maintain the closed state of the RyR channel at the resting state of the skeletal muscle, other cellular mechanisms must be involved. For example, the voltage sensor located on the transverse-tubule membrane has been shown to play an inhibitory role on the RyR function with muscle cells at a polarized state (24Lee E.H. Lopez J.R. Li J. Protasi F. Pessah I.N. Kim D.H. Allen P.D. Am. J. Physiol. 2004; 286: C179-C189Crossref PubMed Scopus (34) Google Scholar). Other cytosolic proteins, such as FKBP12 or calmodulin, have been shown to associate with RyR and to modulate the active state of the Ca2+ release channel (25Meissner G. Biochemistry. 1986; 25: 244-251Crossref PubMed Scopus (111) Google Scholar, 26Meissner G. Front. Biosci. 2002; 7: d2072-d2080Crossref PubMed Google Scholar, 27Gaburjakova M. Gaburjakova J. Reiken S. Huang F. Marx S.O. Rosemblit N. Marks A.R. J. Biol. Chem. 2001; 276: 16931-16935Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar). It remains to be examined how the acute absence of MG29 (e.g. through small interfering RNA-mediated knockdown mechanism) in the adult skeletal muscle affects the overall Ca2+ signaling process in muscle contraction, such as store-operated Ca2+ entry, voltage-induced Ca2+ release, and Ca2+-induced Ca2+ release." @default.
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• W2040595410 title "Co-expression of MG29 and Ryanodine Receptor Leads to Apoptotic Cell Death" @default.
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• W2040595410 cites W1988740497 @default.
• W2040595410 cites W2002208801 @default.
• W2040595410 cites W2028807910 @default.
• W2040595410 cites W2028982808 @default.
• W2040595410 cites W2039547987 @default.
• W2040595410 cites W2039898903 @default.
• W2040595410 cites W2062473966 @default.
• W2040595410 cites W2062508058 @default.
• W2040595410 cites W206588626 @default.
• W2040595410 cites W2068323006 @default.
• W2040595410 cites W2074329998 @default.
• W2040595410 cites W2074986507 @default.
• W2040595410 cites W2075787525 @default.
• W2040595410 cites W2075989491 @default.
• W2040595410 cites W2084314209 @default.
• W2040595410 cites W2085139421 @default.
• W2040595410 cites W2095546957 @default.
• W2040595410 cites W2116214367 @default.
• W2040595410 cites W2137283585 @default.
• W2040595410 cites W2146034579 @default.
• W2040595410 cites W2158114348 @default.
• W2040595410 cites W2341538274 @default.
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