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Azzam Alkhalifah, Henri Montaudié, Jean-Philippe Lacour, Michel Lantéri-Minet, Thierry Passeron
Hailey-Hailey disease, also known as familial benign chronic pemphigus, is a rare autosomal dominant genodermatosis characterized by vesicular lesions, painful erosions, fissures and erythematous plaques occurring at sites of friction. UV exposure, sweating, friction, and cutaneous infection can exacerbate the manifestations (1) . Intracellular signalization abnormalities occur due to mutations of the ATP2C1 gene, the coding calcium ion transporter protein SPCA1 on Golgi apparatus, causing intra-epidermal acantholysis responsible for the clinical manifestations (2) ...
August 11, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
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
M Micaroni, G Giacchetti, R Plebani, G G Xiao, L Federici
ATP2C1 gene codes for the secretory pathway Ca(2+)/Mn(2+)-ATPase pump type 1 (SPCA1) localizing at the golgi apparatus. Mutations on the human ATP2C1 gene, causing decreased levels of the SPCA1 expression, have been identified as the cause of the Hailey-Hailey disease, a rare skin disorder. In the last few years, several mutations have been described, and here we summarize how they are distributed along the gene and how missense mutations affect protein expression. SPCA1 is expressed in four different isoforms through alternative splicing of the ATP2C1 gene and none of these isoforms is differentially affected by any of these mutations...
2016: Cell Death & Disease
Alvaro H Crevenna, Birgit Blank, Andreas Maiser, Derya Emin, Jens Prescher, Gisela Beck, Christine Kienzle, Kira Bartnik, Bianca Habermann, Mehrshad Pakdel, Heinrich Leonhardt, Don C Lamb, Julia von Blume
Sorting and export of transmembrane cargoes and lysosomal hydrolases at the trans-Golgi network (TGN) are well understood. However, elucidation of the mechanism by which secretory cargoes are segregated for their release into the extracellular space remains a challenge. We have previously demonstrated that, in a reaction that requires Ca(2+), the soluble TGN-resident protein Cab45 is necessary for the sorting of secretory cargoes at the TGN. Here, we report that Cab45 reversibly assembles into oligomers in the presence of Ca(2+) These Cab45 oligomers specifically bind secretory proteins, such as COMP and LyzC, in a Ca(2+)-dependent manner in vitro...
May 9, 2016: Journal of Cell Biology
Yongmei Fan, Changjie Zhang, Ting Li, Wenna Peng, Jing Yin, Xiaofao Li, Ying Kong, Chunna Lan, Rumi Wang, Zhiping Hu
BACKGROUND: Short wave (SW), a pattern of electromagnetic therapy, achieves an oscillating electromagnetic field. It has been reported that it may have a potential effect on cerebral injury. The present study was designed to investigate the potential role and possible mechanism of SW in focal cerebral ischemia/reperfusion (I/R) injury in rats. Secretory pathway Ca(2+)/Mn(2+) ATPase isoform 1 is a major component of Golgi apparatus stress. It has been reported as representative of Golgi apparatus stress...
July 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Yongmei Fan, Changjie Zhang, Wenna Peng, Ting Li, Jing Yin, Ying Kong, Chunna Lan, Xiaofang Li, Rumi Wang, Zhiping Hu
The present study was designed to investigate the potential role of secretory pathway Ca2+-ATPase isoform 1(SPCA1) in experimental focal cerebral ischemia-reperfusion injury. Cerebral ischemia-reperfusion was induced by transient middle cerebral artery occlusion (MCAO) for 2 hour s in Sprague-Dawley rats, and then the expression levels of SPAC1 mRNA and protein were determined. Results showed that SPCA1 level was transiently increased 1day after reperfusion in peri-infarction area, while markedly increased in infarction core on 3day and 7day after reperfusion...
March 30, 2016: Brain Research
Donna Dang, Rajini Rao
Ca(2+)-ATPases belonging to the superfamily of P-type pumps play an important role in maintaining low, nanomolar cytoplasmic Ca(2+) levels at rest and priming organellar stores, including the endoplasmic reticulum, Golgi, and secretory vesicles with high levels of Ca(2+) for a wide range of signaling functions. In this review, we introduce the distinct subtypes of Ca(2+)-ATPases and their isoforms and splice variants and provide an overview of their specific cellular roles as they relate to genetic disorders and cancer, with a particular emphasis on recent findings on the secretory pathway Ca(2+)-ATPases (SPCA)...
June 2016: Biochimica et Biophysica Acta
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
Ming Cai, Zhiqiang Wang, Jiru Zhang, Huan Zhou, Linfang Jin, Ruizhen Bai, Yuan Weng
BACKGROUND/AIMS: A disintegrin and metalloprotease (ADAM) 17 has been reported to be implicated in cancer cells invasion. Nevertheless, its potential role in lung adenocarcinoma has not been addressed clearly. METHODS: RT-PCR and Western blot were used to detect the expression of miR-326 and ADAM17 in lung adenocarcinoma samples (n=73). miR-326 mimics and inhibitor were tansfected in human A549 and SPCA1 cell lines. The transwell assay was used to detect the cell invasive ability...
2015: Cellular Physiology and Biochemistry
Xueying Yang, Fushuang Zheng, Suning Zhang, Jibin Lu
Lung cancer is the leading cause of cancer-related death worldwide, mainly due to its highly metastatic properties. Previously, we reported an inverse correlation between Rho-kinase inhibitor and the progression of the lung cancer cells. The purpose of this study was to investigate the effects of RhoA on the proliferation, adhesion, invasion, and migration of SPCA1 lung carcinoma cells and to explore the underlying molecular mechanisms. RNA interference was used to downregulate RhoA expression in these cells...
February 2015: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Francisco J Aulestia, María Teresa Alonso, Javier García-Sancho
High Ca2+ content in the Golgi apparatus (Go) is essential for protein processing and sorting. In addition, the Go can shape the cytosolic Ca2+ signals by releasing or sequestering Ca2+. We generated two new aequorin-based Ca2+ probes to specifically measure Ca2+ in the cis/cis-to-medial-Go (cGo) or the trans-Go (tGo). Ca2+ homoeostasis in these compartments and in the endoplasmic reticulum (ER) has been studied and compared. Moreover, the relative size of each subcompartment was estimated from aequorin consumption...
March 15, 2015: Biochemical Journal
Alessandro Borghi, Alessandro Rimessi, Sara Minghetti, Monica Corazza, Paolo Pinton, Annarosa Virgili
BACKGROUND: Hailey-Hailey disease (HHD), also known as familial benign chronic pemphigus, is a rare autosomal dominant inherited intraepidermal blistering genodermatosis. Mutations in the ATP2C1 gene encoding for the Golgi secretory pathway Ca(2+) /Mn(2+) -ATPasi protein 1 (SPCA1) affect the processing of desmosomal components and the epidermal suprabasal cell-cell adhesion by deregulating the keratinocyte cytosolic Ca(2+) concentration. We report the unexpected, dramatic, and persistent clinical improvement of the skin lesions of a patient affected with longstanding HHD with daily intake of a solution containing magnesium chloride hexahydrate (MgCl2 )...
2015: International Journal of Dermatology
Jimena Laporta, Kimberly P Keil, Chad M Vezina, Laura L Hernandez
Lactation is characterized by massive transcellular flux of calcium, from the basolateral side of the mammary alveolar epithelium (blood) into the ductal lumen (milk). Regulation of calcium transport during lactation is critical for maternal and neonatal health. The monoamine serotonin (5-HT) is synthesized by the mammary gland and functions as a homeostatic regulation of lactation. Genetic ablation of tryptophan hydroxylase 1 (Tph1), which encodes the rate-limiting enzyme in non-neuronal serotonin synthesis, causes a deficiency in circulating serotonin...
2014: PloS One
Dingwei Zhang, Xiaoli Li, Zhenghui Wang, Yanfei Zhang, Kun Guo, Shuang Wang, Chen Tu, Jia Huo, Shengxiang Xiao
Hailey-Hailey disease (HHD) is caused by heterozygous mutations in the ATP2C1 gene, encoding the secretory pathway Ca(2+) ATPase1 (SPCA1). SPCA1 and sarco/endoplasmic reticulum Ca(2+) ATPase2 (SERCA2) encoded by ATP2A2 are two essential calcium pumps needed for Ca(2+) homeostasis maintenance in keratinocytes. ATP2A2 mutations cause another hereditary skin disorder, Darier's disease (DD). Previously, the compensatory expression of SPCA1 for SERCA2 insufficiency in DD was demonstrated, but it is not known whether a similar compensatory mechanism exists in HHD...
March 2015: Archives of Dermatological Research
Christine Kienzle, Nirakar Basnet, Alvaro H Crevenna, Gisela Beck, Bianca Habermann, Naoko Mizuno, Julia von Blume
The actin filament severing protein cofilin-1 (CFL-1) is required for actin and P-type ATPase secretory pathway calcium ATPase (SPCA)-dependent sorting of secretory proteins at the trans-Golgi network (TGN). How these proteins interact and activate the pump to facilitate cargo sorting, however, is not known. We used purified proteins to assess interaction of the cytoplasmic domains of SPCA1 with actin and CFL-1. A 132-amino acid portion of the SPCA1 phosphorylation domain (P-domain) interacted with actin in a CFL-1-dependent manner...
September 1, 2014: Journal of Cell Biology
Christine Kienzle, Julia von Blume
Sorting of proteins for secretion from cells is crucial for normal physiology and the regulation of key cellular events. Although the sorting of lysosomal hydrolases at the trans-Golgi network (TGN) for delivery to pre-lysosomes is well characterized, the corresponding mechanism by which secreted proteins are sorted for plasma-membrane delivery remains poorly understood. Recent discoveries have revealed a novel sorting mechanism that requires the linkage between the cytoplasmic actin cytoskeleton to the membrane-anchored Ca(2+) ATPase, SPCA1 (secretory pathway calcium ATPase 1), and the luminal 45 kDa Ca(2+)-binding protein, Cab45, for successful sorting of a subset of proteins at the TGN...
October 2014: Trends in Cell Biology
Timothy A Reinhardt, John D Lippolis, Randy E Sacco
Plasma membrane Ca(2+)-ATPase 2 (PMCA2) knockout mice showed that ~60% of calcium in milk is transported across the mammary cells apical membrane by PMCA2. The remaining milk calcium is thought to arrive via the secretory pathway through the actions of secretory pathway Ca(2+)-ATPase's 1 and/or 2 (SPCA1 and 2). However, another secretory pathway calcium transporter was recently described. The question becomes whether this Golgi Ca(2+)/H(+) antiporter (TMEM165) is expressed sufficiently in the Golgi of lactating mammary tissue to be a relevant contributor to secretory pathway mammary calcium transport...
March 7, 2014: Biochemical and Biophysical Research Communications
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
Yunying Zhao, Jingcai Du, Bing Xiong, Huihui Xu, Linghuo Jiang
The endosomal sorting complex required for transport (ESCRT) complexes function to form multivesicular bodies for sorting of proteins destined for the yeast vacuole or the mammalian lysosome. ESCRT components are well conserved in eukaryotes, and their mutations cause neurodegenerative diseases and other cellular pathologies in humans. PMR1 is the orthologous gene of two human genes for calcium pumps secretory pathway Ca(2+)-ATPase (SPCA1, ATP2C1) and sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA, ATP2A2), which are mutated in Hailey-Hailey and Darier genetic diseases, respectively...
October 2013: Journal of Molecular Cell Biology
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
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