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https://www.readbyqxmd.com/read/27692665/spca2-couples-ca-2-influx-via-orai1-to-ca-2-uptake-into-the-golgi-secretory-pathway
#1
Susanne Smaardijk, Jialin Chen, Frank Wuytack, Peter Vangheluwe
Dysregulation of the Golgi/Secretory Pathway Ca(2+) transport ATPase SPCA2 is implicated in breast cancer. During lactation and in luminal breast cancer types, SPCA2 interacts with the plasma membrane Ca(2+) channel Orai1, promoting constitutive Ca(2+) influx, which is termed store independent Ca(2+) entry (SICE). The mechanism of SPCA2/Orai1 interaction depends on the N- and C-termini of SPCA2. These extensions may play a dual role in activating not only Orai1, but also Ca(2+) transport into the Golgi/secretory pathway, which we tested by investigating the impact of various SPCA2 N- and/or C-terminal truncations on SICE and Ca(2+) transport activity of SPCA2...
September 17, 2016: Tissue & Cell
https://www.readbyqxmd.com/read/27316461/the-ca2-mn2-transporting-spca2-pump-is-regulated-by-oxygen-and-cell-density-in-colon-cancer-cells
#2
James Jenkins, Dmitri B Papkovsky, Ruslan I Dmitriev
The mammalian SPCA1 and SPCA2 ATPases localize in membranes of the secretory pathway and transport ions of Ca(2+) and Mn(2+) The role of tissue-specific SPCA2 isoform, highly expressed in lungs, mammary gland and gastrointestinal tract, is poorly understood. To elucidate the function of SPCA2, we studied human colon cancer HCT116 cells, grown under ambient and decreased O2 levels. We found that in contrast with other Ca(2+)-ATPase isoforms the expression of SPCA2 was up-regulated under hypoxia (3% O2), in both adherent (2D) and spheroid (3D) cultures...
August 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27297103/identification-of-novel-inhibitors-of-human-spca2
#3
Sachiko Yamamoto, Munenori Takehara, Yoshiki Kabashima, Toshiyuki Fukutomi, Makoto Ushimaru
To identify specific inhibitors of the human secretary pathway Ca(2+)-ATPase 2 (hSPCA2), a recombinant hSPCA2 was expressed in Saccharomyces cerevisiae, and purified by Co(2+)-chelating chromatography. The isolated hSPCA2 catalyzed ATP hydrolysis in the presence of Ca(2+) ions. The Ca(2+) dissociation constant for ATPase activation was 25 nM. hSPCA2 activity was inhibited by thapsigargin, 2,2'-methylenebis(6-tert-butyl-p-cresol), and 4-octylphenol in the low-micromolar concentration range. Unexpectedly, the organic solvent wash from standard laboratory polypropylene microtubes showed strong inhibitory potency toward hSPCA2 activity...
August 19, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27017909/atp2c2-is-transcribed-from-a-unique-transcriptional-start-site-in-mouse-pancreatic-acinar-cells
#4
Melissa A Fenech, Caitlin M Sullivan, Lucimar T Ferreira, Rashid Mehmood, William A MacDonald, Peter B Stathopulos, Christopher L Pin
Proper regulation of cytosolic Ca(2+) is critical for pancreatic acinar cell function. Disruptions in normal Ca(2+) concentrations affect numerous cellular functions and are associated with pancreatitis. Membrane pumps and channels regulate cytosolic Ca(2+) homeostasis by promoting rapid Ca(2+) movement. Determining how expression of Ca(2+) modulators is regulated and the cellular alterations that occur upon changes in expression can provide insight into initiating events of pancreatitis. The goal of this study was to delineate the gene structure and regulation of a novel pancreas-specific isoform for Secretory Pathway Ca(2+) ATPase 2 (termed SPCA2C), which is encoded from the Atp2c2 gene...
December 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/26247838/the-effect-of-tgf-beta-induced-epithelial-mesenchymal-transition-on-the-expression-of-intracellular-calcium-handling-proteins-in-t47d-and-mcf-7-human-breast-cancer-cells
#5
Shah H A Mahdi, Huanyi Cheng, Jinfeng Li, Renqing Feng
The contribution of Ca(2+) in TGF-β-induced EMT is poorly understood. We aimed to confirm the effect of TGF-β on the gene expression of intracellular calcium-handling proteins and to investigate the potential underlying mechanisms in TGF-β-induced EMT. T47D and MCF-7 cells were cultured in vitro and treated with TGF-β. The mRNA expression of EMT marker genes and intracellular calcium-handling proteins were quantified by qRT-PCR. qRT-PCR and Western blot analysis results verified the changes of EMT marker gene expression...
October 1, 2015: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/24359162/assessment-of-orai1-mediated-basal-calcium-influx-in-mammary-epithelial-cells
#6
Diana G F Ross, Chanel E Smart, Iman Azimi, Sarah J Roberts-Thomson, Gregory R Monteith
BACKGROUND: The entry of calcium ions into mammary gland epithelial cells is one of the least well-understood processes in the transport of calcium into milk during lactation. The store-operated calcium entry channel ORAI1, has been suggested as a potential mechanism for the entry of Ca(2+) into mammary gland epithelial cells from the maternal blood supply during lactation. The down regulation of the canonical ORAI1 activator STIM1 during lactation suggests that other known ORAI activators such as STIM2 and SPCA2 may be important during lactation...
December 20, 2013: BMC Cell Biology
https://www.readbyqxmd.com/read/24209443/manganese-and-the-brain
#7
REVIEW
Karin Tuschl, Philippa B Mills, Peter T Clayton
Manganese (Mn) is an essential trace metal that is pivotal for normal cell function and metabolism. Its homeostasis is tightly regulated; however, the mechanisms of Mn homeostasis are poorly characterized. While a number of proteins such as the divalent metal transporter 1, the transferrin/transferrin receptor complex, the ZIP family metal transporters ZIP-8 and ZIP-14, the secretory pathway calcium ATPases SPCA1 and SPCA2, ATP13A2, and ferroportin have been suggested to play a role in Mn transport, the degree that each of them contributes to Mn homeostasis has still to be determined...
2013: International Review of Neurobiology
https://www.readbyqxmd.com/read/23890218/assessment-of-gene-expression-of-intracellular-calcium-channels-pumps-and-exchangers-with-epidermal-growth-factor-induced-epithelial-mesenchymal-transition-in-a-breast-cancer-cell-line
#8
Felicity M Davis, Michelle T Parsonage, Peter J Cabot, Marie-Odile Parat, Erik W Thompson, Sarah J Roberts-Thomson, Gregory R Monteith
BACKGROUND: Epithelial-mesenchymal transition (EMT) is a process implicated in cancer metastasis that involves the conversion of epithelial cells to a more mesenchymal and invasive cell phenotype. In breast cancer cells EMT is associated with altered store-operated calcium influx and changes in calcium signalling mediated by activation of cell surface purinergic receptors. In this study, we investigated whether MDA-MB-468 breast cancer cells induced to undergo EMT exhibit changes in mRNA levels of calcium channels, pumps and exchangers located on intracellular calcium storing organelles, including the Golgi, mitochondria and endoplasmic reticulum (ER)...
2013: Cancer Cell International
https://www.readbyqxmd.com/read/23840669/spca2-regulates-orai1-trafficking-and-store-independent-ca2-entry-in-a-model-of-lactation
#9
Brandie M Cross, Anniesha Hack, Timothy A Reinhardt, Rajini Rao
An unconventional interaction between SPCA2, an isoform of the Golgi secretory pathway Ca(2+)-ATPase, and the Ca(2+) influx channel Orai1, has previously been shown to contribute to elevated Ca(2+) influx in breast cancer derived cells. In order to investigate the physiological role of this interaction, we examined expression and localization of SPCA2 and Orai1 in mouse lactating mammary glands. We observed co-induction and co-immunoprecipitation of both proteins, and isoform-specific differences in the localization of SPCA1 and SPCA2...
2013: PloS One
https://www.readbyqxmd.com/read/23670239/new-insights-into-store-independent-ca-2-entry-secretory-pathway-calcium-atpase-2-in-normal-physiology-and-cancer
#10
REVIEW
Ming-Ye Feng, Rajini Rao
Recent studies in secretory pathway calcium ATPases (SPCA) revealed novel functions of SPCA2 in interacting with store-operated Ca(2+) channel Orai1 and inducing Ca(2+) influx at the cell surface. Importantly, SPCA2-mediated Ca(2+) signaling is uncoupled from its conventional role of Ca(2+)-ATPase and independent of store-operated Ca(2+) signaling pathway. SPCA2-induced store-independent Ca(2+) entry (SICE) plays essential roles in many important physiological processes, while unbalanced SICE leads to enhanced cell proliferation and tumorigenesis...
June 2013: International Journal of Oral Science
https://www.readbyqxmd.com/read/22888420/prolactin-and-dexamethasone-regulate-second-messenger-stimulated-cl-secretion-in-mammary-epithelia
#11
Utchariya Anantamongkol, Mei Ao, Jayashree Sarathy Nee Venkatasubramanian, Y Sangeeta Devi, Nateetip Krishnamra, Mrinalini C Rao
Mammary gland ion transport is essential for lactation and is regulated by prolactin and glucocorticoids. This study delineates the roles of prolactin receptors (PRLR) and long-term prolactin and dexamethasone (P-D)-mediation of [Ca(2+)](i) and Cl(-) transport in HC-11 cells. P-D (24 h) suppressed ATP-induced [Ca(2+)](i). This may be due to decreased Ca(2+) entry since P-D decreased transient receptor potential channel 3 (TRPC3) but not secretory pathway Ca(2+)-ATPase 2 (SPCA2) mRNA. ATP increased Cl(-) transport, measured by iodide (I(-)) efflux, in control and P-D-treated cells...
2012: Journal of Signal Transduction
https://www.readbyqxmd.com/read/22240025/structural-evolution-and-tissue-specific-expression-of-tetrapod-specific-second-isoform-of-secretory-pathway-ca2-atpase
#12
Nikolay B Pestov, Ruslan I Dmitriev, Maria B Kostina, Tatyana V Korneenko, Mikhail I Shakhparonov, Nikolai N Modyanov
Secretory pathway Ca-ATPases are less characterized mammalian calcium pumps than plasma membrane Ca-ATPases and sarco-endoplasmic reticulum Ca-ATPases. Here we report analysis of molecular evolution, alternative splicing, tissue-specific expression and subcellular localization of the second isoform of the secretory pathway Ca-ATPase (SPCA2), the product of the ATP2C2 gene. The primary structure of SPCA2 from rat duodenum deduced from full-length transcript contains 944 amino acid residues, and exhibits 65% sequence identity with known SPCA1...
January 27, 2012: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/21674634/secretory-pathway-stress-responses-as-possible-mechanisms-of-disease-involving-golgi-ca2-pump-dysfunction
#13
REVIEW
Gary E Shull, Marian L Miller, Vikram Prasad
In mammalian tissues, uptake of Ca(2+) and Mn(2+) by Golgi membranes is mediated by the secretory pathway Ca(2+) -ATPases, SPCA1 and SPCA2, encoded by the ATP2C1 and ATP2C2 genes. Loss of one copy of the ATP2C1 gene, which causes SPCA1 haploinsufficiency, leads to squamous cell tumors of keratinized epithelia in mice and to Hailey-Hailey disease, an acantholytic skin disease, in humans. Although the disease phenotypes resulting from SPCA1 haploinsufficiency in mice and humans are quite different, each species-specific phenotype is remarkably similar to those arising as a result of null mutations in one copy of the ATP2A2 gene, encoding SERCA2, the endoplasmic reticulum (ER) Ca(2+) pump...
May 2011: BioFactors
https://www.readbyqxmd.com/read/20887894/store-independent-activation-of-orai1-by-spca2-in-mammary-tumors
#14
Mingye Feng, Desma M Grice, Helen M Faddy, Nguyen Nguyen, Sharon Leitch, Yingyu Wang, Sabina Muend, Paraic A Kenny, Saraswati Sukumar, Sarah J Roberts-Thomson, Gregory R Monteith, Rajini Rao
Ca(2+) is an essential and ubiquitous second messenger. Changes in cytosolic Ca(2+) trigger events critical for tumorigenesis, such as cellular motility, proliferation, and apoptosis. We show that an isoform of Secretory Pathway Ca(2+)-ATPase, SPCA2, is upregulated in breast cancer-derived cells and human breast tumors, and suppression of SPCA2 attenuates basal Ca(2+) levels and tumorigenicity. Contrary to its conventional role in Golgi Ca(2+) sequestration, expression of SPCA2 increased Ca(2+) influx by a mechanism dependent on the store-operated Ca(2+) channel Orai1...
October 1, 2010: Cell
https://www.readbyqxmd.com/read/20599950/mist1-regulates-the-pancreatic-acinar-cell-expression-of-atp2c2-the-gene-encoding-secretory-pathway-calcium-atpase-2
#15
Victoria C Garside, Agnes S Kowalik, Charis L Johnson, Daniel DiRenzo, Stephen F Konieczny, Christopher L Pin
MIST1 is a transcription factor expressed in pancreatic acinar cells and other serous exocrine cells. Mice harboring a targeted deletion of the Mist1 gene (Mist1(-/-)) exhibit alterations in acinar regulated exocytosis and aberrant Ca(2+) signaling that are normally controlled by acinar cell Ca(2+)-ATPases. Previous studies indicated that total sarcoendoplasmic reticulum Ca(2+)-ATPases (SERCA) and plasma membrane Ca(2+)-ATPases (PMCA) remained unaffected in Mist1(-/-) acinar cultures. Therefore, we have assessed the expression of Atp2c2, the gene that encodes the secretory pathway Ca(2+)-ATPase 2 (SPCA2)...
October 15, 2010: Experimental Cell Research
https://www.readbyqxmd.com/read/20363212/the-secretory-pathway-ca-2-atpase-1-is-associated-with-cholesterol-rich-microdomains-of-human-colon-adenocarcinoma-cells
#16
Szilvia Baron, Peter Vangheluwe, Maria Rosario Sepúlveda, Frank Wuytack, Luc Raeymaekers, Jo Vanoevelen
Lipid rafts are often considered as microdomains enriched in sphingomyelin and cholesterol, predominantly residing in the plasma membrane but which originate in earlier compartments of the cellular secretory pathway. Within this pathway, the membranes of the Golgi complex represent a transition stage between the cholesterol-poor membranes of the endoplasmic reticulum (ER) and the cholesterol-rich plasma membrane. The rafts are related to detergent-resistant membranes, which because of their ordered structure are poorly penetrated by cold non-ionic detergents and float in density gradient centrifugation...
August 2010: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/19000904/mammary-gland-involution-is-associated-with-rapid-down-regulation-of-major-mammary-ca2-atpases
#17
Timothy A Reinhardt, John D Lippolis
Sixty percent of calcium in milk is transported across the mammary cells apical membrane by the plasma membrane Ca(2+)-ATPase 2 (PMCA2). The effect of abrupt cessation of milk production on the Ca(2+)-ATPases and mammary calcium transport is unknown. We found that 24 h after stopping milk production, PMCA2 and secretory pathway Ca(2+)-ATPases 1 and 2 (SPCA1 and 2) expression decreased 80-95%. PMCA4 and Sarco/Endoplasmic Reticulum Ca(2+)-ATPase 2 (SERCA2) expression increased with the loss of PMCA2, SPCA1, and SPCA2 but did not increase until 72-96 h of involution...
January 2, 2009: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/18392750/hepatic-cirrhosis-dystonia-polycythaemia-and-hypermanganesaemia-a-new-metabolic-disorder
#18
Karin Tuschl, Philippa B Mills, Howard Parsons, Marian Malone, Darren Fowler, Maria Bitner-Glindzicz, Peter T Clayton
We report a new constellation of clinical features consisting of hypermanganesaemia, liver cirrhosis, an extrapyramidal motor disorder and polycythaemia in a 12 year-old girl born to consanguineous parents. Blood manganese levels were >3000 nmol/L (normal range <320 nmol/L) and MRI revealed signal abnormalities of the basal ganglia consistent with manganese deposition. An older brother with the same phenotype died at 18 years, suggesting a potentially lethal, autosomal recessive disease. This disorder is probably caused by a defect of manganese metabolism with the accumulation of manganese in the liver and the basal ganglia similar to the copper accumulation in Wilson disease...
April 2008: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/18334228/localization-of-plasma-membrane-and-secretory-calcium-pumps-in-the-mammary-gland
#19
Helen M Faddy, Chanel E Smart, Ren Xu, Genee Y Lee, Paraic A Kenny, Mingye Feng, Rajini Rao, Melissa A Brown, Mina J Bissell, Sarah J Roberts-Thomson, Gregory R Monteith
Until recently the mechanism for the enrichment of milk with calcium was thought to be almost entirely via the secretory pathway. However, recent studies suggest that a plasma membrane calcium ATPase, PMCA2, is the primary mechanism for calcium transport into milk, highlighting a major role for apical calcium transport. We compared the expression of the recently identified secretory calcium ATPase, SPCA2, and SPCA1, in the mouse mammary gland during development. SPCA2 levels increased over 35-fold during lactation with expression localized to luminal secretory cells, while SPCA1 increased only a modest 2-fold and was expressed throughout the cells of the mammary gland...
May 9, 2008: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/17129574/regulation-of-ca2-mobilization-by-prolactin-in-mammary-gland-cells-possible-role-of-secretory-pathway-ca2-atpase-type-2
#20
Utchariya Anantamongkol, Haruo Takemura, Tuangporn Suthiphongchai, Nateetip Krishnamra, Yoshiyuki Horio
Regulatory role of prolactin (PRL) on Ca2+ mobilization in human mammary gland cell line MCF-7 was examined. Direct addition of PRL did not affect cytoplasmic Ca2+ concentration ([Ca2+]i); however, treatment with PRL for 24h significantly decreased the peak level and duration time of [Ca2+]i elevation evoked by ATP or thapsigargin (TG). Intracellular Ca2+ release by IP3 or TG in permeablized cells was not decreased after PRL-treatment, indicating that the Ca2+ release was not impaired by PRL treatment. Extracellular Ca2+ entry evoked by ATP or TG was likely to be intact, because entry of extracellular Ba2+ was not affected by PRL treatment...
January 12, 2007: Biochemical and Biophysical Research Communications
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