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Valerie Matagne, Joyce Wondolowski, Matthew Frerking, Mohammad Shahidullah, Nicholas A Delamere, Ursula S Sandau, Sarojini Budden, Sergio R Ojeda
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the MECP2 gene. In the absence of MeCP2/MECP2, expression of FXYD domain-containing transport regulator 1 (FXYD1) is deregulated in the frontal cortex (FC) of mice and humans. Because FXYD1 is a membrane protein that controls cell excitability by modulating Na+ , K+ -ATPase activity (NKA), an excess of FXYD1 may reduce NKA activity and contribute to the neuronal phenotype of Mecp2 deficient (KO) mice. To determine if FXYD1 can rescue these RTT deficits, we studied the male progeny of Fxyd1 null males bred to heterozygous Mecp2 female mice...
June 11, 2018: Brain Research
Boris Chaumette, Vladimir Ferrafiat, Amirthagowri Ambalavanan, Alice Goldenberg, Alexandre Dionne-Laporte, Dan Spiegelman, Patrick A Dion, Priscille Gerardin, Claudine Laurent, David Cohen, Judith Rapoport, Guy A Rouleau
Childhood-onset schizophrenia (COS) is a rare and severe form of schizophrenia defined as onset before age of 13. Here we report on two unrelated cases diagnosed with both COS and alternating hemiplegia of childhood (AHC), and for whom two distinct pathogenic de novo variants were identified in the ATP1A3 gene. ATP1A3 encodes the α-subunit of a neuron-specific ATP-dependent transmembrane sodium-potassium pump. Using whole exome sequencing data derived from a cohort of 17 unrelated COS cases, we also examined ATP1A3 and all of its interactors known to be expressed in the brain to establish if variants could be identified...
June 12, 2018: Molecular Psychiatry
Li-Juan Wang, Qi-Jiong Li, Yong Le, Han-Yue Ouyang, Min-Ke He, Zi-Shan Yu, Yong-Fa Zhang, Ming Shi
The clinical significance of the sodium-potassium ATPase regulator FXYD domain-containing ion transport regulator 3 (FXYD3) has been demonstrated in a number of types of cancer. However, the role of this protein in human hepatocellular carcinoma (HCC) remains to be elucidated. In the present study, 217 HCC tissue samples were analyzed to evaluate the expression and prognostic significance of FXYD3 in HCC. Reverse transcription-quantitative polymerase chain reaction was used to analyze the mRNA expression of FXYD3 in 80 primary HCC specimens and paired non-cancerous liver tissue samples, while western blotting was used to analyze the protein expression level of FXYD3 in another 24 pairs...
March 2018: Oncology Letters
Xuefeng Li, Yu Liang, Zhili Qiao, Jiaoxia Yang, Pengfei Han, Binghai Zhao, Fengxiang Li, Hengjuan Lv, Jifang Guo, Fengmin Gao, Li Li
The aim of this study was to explore how atrial natriuretic polypeptide (ANP) affects the properties and function of endothelial cells. Gene expression data GSE56976 generated at 0, 1, and 6 hours after ANP incubation in human umbilical vein endothelial cells (HUVEC) was used. Microarray data were preprocessed for differentially expressed genes (DEGs) in each time-dependent group. Next, gene ontology (GO), pathway analysis, and transcriptional regulation were performed. Co-expression clustering analysis of DEGs and functional enrichment analysis of co-expression modules were processed...
January 27, 2018: International Heart Journal
Surajit Pathak, Antara Banerjee, Wen-Jian Meng, Suman Kumar Nandy, Madhumala Gopinath, Xiao-Feng Sun
AIM: To demonstrate the radiation responses of tafazzin (TAZ) protein in colon cancer. METHODS: TAZ expression was examined in colon cancer cell lines SW480, KM12C, SW620 and KM12L4a. KM12C and KM12L4a cell lines were used for this experiment with exposure to X- and UV rays (mW/cm2 ). HCT15 cell line was used to test the expression of TAZ by using an anti-TAZ drug, namely 9-fluorenone, which is a Hippo-YAP/TAZ signaling inhibitor. The experimentation also involved exposing HCT15 cell line, to UV radiation...
January 2018: International Journal of Radiation Biology
Ying-Ying Chen, Xiao-Ying Wang, Qiu-Xia Fu, Yi Kang, He-Bin Yao
The pathogenesis of hypokalemic periodic paralysis (HypoPP) remains unclear. Though some mutations in skeletal muscle ion channels were revealed previously, the exact mechanism remains to be fully elucidated. Increased Na(+)/K(+)-ATPase activity in skeletal muscle is postulated to contribute to attacks of HypoPP. Before the link between Na(+)/K(+)-ATPase dysfunction and these ion channel mutations is established, mutations in Na(+)/K(+)-ATPase and their regulators are the first to be excluded. Phospholemman, which is a protein encoded by the FXYD domain-containing ion transport regulator 1 (FXYD1) gene, is predominantly expressed in skeletal muscle and is the major regulator of Na(+)/K(+)-ATPase...
October 2017: Experimental and Therapeutic Medicine
Michael V Clausen, Florian Hilbers, Hanne Poulsen
The sodium and potassium gradients across the plasma membrane are used by animal cells for numerous processes, and the range of demands requires that the responsible ion pump, the Na,K-ATPase, can be fine-tuned to the different cellular needs. Therefore, several isoforms are expressed of each of the three subunits that make a Na,K-ATPase, the alpha, beta and FXYD subunits. This review summarizes the various roles and expression patterns of the Na,K-ATPase subunit isoforms and maps the sequence variations to compare the differences structurally...
2017: Frontiers in Physiology
Sergej Pirkmajer, Henriette Kirchner, Leonidas S Lundell, Pavel V Zelenin, Juleen R Zierath, Kira S Makarova, Yuri I Wolf, Alexander V Chibalin
KEY POINTS: Small transmembrane proteins such as FXYDs, which interact with Na+ ,K+ -ATPase, and the micropeptides that interact with sarco/endoplasmic reticulum Ca2+ -ATPase play fundamental roles in regulation of ion transport in vertebrates. Uncertain evolutionary origins and phylogenetic relationships among these regulators of ion transport have led to inconsistencies in their classification across vertebrate species, thus hampering comparative studies of their functions. We discovered the first FXYD homologue in sea lamprey, a basal jawless vertebrate, which suggests small transmembrane regulators of ion transport emerged early in the vertebrate lineage...
July 15, 2017: Journal of Physiology
Michael Habeck, Einat Kapri-Pardes, Michal Sharon, Steven J D Karlish
Membrane protein function can be affected by the physical state of the lipid bilayer and specific lipid-protein interactions. For Na,K-ATPase, bilayer properties can modulate pump activity, and, as observed in crystal structures, several lipids are bound within the transmembrane domain. Furthermore, Na,K-ATPase activity depends on phosphatidylserine (PS) and cholesterol, which stabilize the protein, and polyunsaturated phosphatidylcholine (PC) or phosphatidylethanolamine (PE), known to stimulate Na,K-ATPase activity...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
Wen-Kai Yang, Chao-Kai Kang, An-Di Hsu, Chia-Hao Lin, Tsung-Han Lee
Upon salinity challenge, the Na(+)-K(+)-ATPase (NKA) of fish kidney plays a crucial role in maintaining ion and water balance. Moreover, the FXYD protein family was found to be a regulator of NKA. Our preliminary results revealed that fxyd12 was highly expressed in the kidneys of the two closely related euryhaline medaka species (Oryzias dancena and O. latipes) from different natural habitats (brackish water and fresh water). In this study, we investigated the expression and association of renal FXYD12 and NKA α-subunit as well as potential functions of FXYD12 in the two medakas...
2016: International Journal of Biological Sciences
Per Loftas, Gunnar Arbman, Xiao-Feng Sun, David Edler, Erik Syk, Olof Hallbook
PURPOSE: In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer. MATERIALS AND METHODS: FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48)...
March 2016: Radiation Oncology Journal
Elena Arystarkhova
The fundamental role of Na,K-ATPase in eukaryotic cells calls for complex and efficient regulation of its activity. Besides alterations in gene expression and trafficking, kinetic properties of the pump are modulated by reversible association with single span membrane proteins, the FXYDs. Seven members of the family are expressed in a tissue-specific manner, affecting pump kinetics in all possible permutations. This mini-review focuses on functional properties of FXYD2 studied in transfected cells, and on noteworthy and unexpected phenotypes discovered in a Fxyd2 (-∕-) mouse...
2016: Frontiers in Physiology
Irina Lubarski-Gotliv, Carol Asher, Laura A Dada, Haim Garty
The FXYD proteins are a family of small membrane proteins that share an invariant four amino acid signature motif F-X-Y-D and act as tissue-specific regulatory subunits of the Na,K-ATPase. FXYD5 (also termed dysadherin or RIC) is a structurally and functionally unique member of the FXYD family. As other FXYD proteins, FXYD5 specifically interacts with the Na,K-ATPase and alters its kinetics by increasing Vmax However, unlike other family members FXYD5 appears to have additional functions, which cannot be readily explained by modulation of transport kinetics...
May 20, 2016: Journal of Biological Chemistry
Chia-Hao Chang, Wen-Kai Yang, Chia-Hao Lin, Chao-Kai Kang, Cheng-Hao Tang, Tsung-Han Lee
FXYD proteins regulate Na(+)/K(+)-ATPase (NKA), which is a primary active pump that provides the driving force that triggers osmoregulatory systems in teleosts. To explore the regulatory mechanisms between FXYD and NKA in euryhaline teleosts, the expression of NKA (mRNA, protein, and activity) and FXYD11 and their interaction were examined in the gills of brackish medaka (Oryzias dancena) when transferred from brackish water (BW; 15‰) to fresh water (FW) or seawater (SW; 35‰). The mRNA expression of Odfxyd11 and Odnka-α was elevated 48h post-hypoosmotic transfer...
April 2016: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Márta Sárközy, Gergő Szűcs, Márton Pipicz, Ágnes Zvara, Katalin Éder, Veronika Fekete, Csilla Szűcs, Judit Bárkányi, Csaba Csonka, László G Puskás, Csaba Kónya, Péter Ferdinandy, Tamás Csont
BACKGROUND: Diabetic patients have an increased risk of developing cardiovascular diseases, which are the leading cause of death in developed countries. Although multivitamin products are widely used as dietary supplements, the effects of these products have not been investigated in the diabetic heart yet. Therefore, here we investigated if a preparation of different minerals, vitamins, and trace elements (MVT) affects the cardiac gene expression pattern in experimental diabetes. METHODS: Two-day old male Wistar rats were injected with streptozotocin (i...
2015: Cardiovascular Diabetology
F Cornelius, M Habeck, R Kanai, C Toyoshima, S J D Karlish
The molecular activity of Na,K-ATPase and other P2 ATPases like Ca(2+)-ATPase is influenced by the lipid environment via both general (physical) and specific (chemical) interactions. Whereas the general effects of bilayer structure on membrane protein function are fairly well described and understood, the importance of the specific interactions has only been realized within the last decade due particularly to the growing field of membrane protein crystallization, which has shed new light on the molecular details of specific lipid-protein interactions...
September 2015: Biochimica et Biophysica Acta
Rocío Retamales-Ortega, Carlos P Vio, Nibaldo C Inestrosa
P2C-type ATPases are a subfamily of P-type ATPases comprising Na(+)/K(+)-ATPase and H(+)/K(+)-ATPase. Na(+)/K(+)-ATPase is ubiquitously expressed and has been implicated in several neurological diseases, whereas H(+)/K(+)-ATPase is found principally in the colon, stomach, and kidney. Both ATPases have two subunits, α and β, but Na(+)/K(+)-ATPase also has a regulatory subunit called FXYD, which has an important role in cancer. The most important functions of these ATPases are homeostasis, potassium regulation, and maintaining a gradient in different cell types, like epithelial cells...
March 2016: Molecular Neurobiology
Elena Arystarkhova, Donna L Ralph, Yi Bessie Liu, Richard Bouley, Alicia A McDonough, Kathleen J Sweadner
Na,K-ATPase generates the driving force for sodium reabsorption in the kidney. Na,K-ATPase functional properties are regulated by small proteins belonging to the FXYD family. In kidney FXYD2 is the most abundant: it is an inhibitory subunit expressed in almost every nephron segment. Its absence should increase sodium pump activity and promote Na(+) retention, however, no obvious renal phenotype was detected in mice with global deletion of FXYD2 (Arystarkhova et al. 2013). Here, increased total cortical Na,K-ATPase activity was documented in the Fxyd2(-/-) mouse, without increased α1β1 subunit expression...
December 1, 2014: Physiological Reports
Pan Hu, Siqi Li, Yong Zhong, Xingjiang Mu, Lang Gui, Junbin Zhang
By interacting with Na(+), K(+)-ATPase (NKA), the FXYD domain-containing ion transport regulator (FXYD) is involved in teleost osmoregulation, but knowledge of FXYD in marine fish is limited. In the present study, fxyd11 and fxyd12 were identified from the spotted scat (Scatophagus argus), and the two members of the FXYD protein family were expressed in a tissue-specific manner. Fxyd11 mRNA was predominantly expressed in gills, whereas fxyd12 mRNA was mainly distributed in kidneys and intestines. Acute hyposaline stress altered the activity of NKA and the expression of fxyd11 and fxyd12 in gills, kidneys, and intestines...
August 2014: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Surajit Pathak, Wen-Jian Meng, Hong Zhang, Sebastian Gnosa, Suman Kumar Nandy, Gunnar Adell, Birgitta Holmlund, Xiao-Feng Sun
BACKGROUND: Tafazzin (TAZ), a transmembrane protein contributes in mitochondrial structural and functional modifications through cardiolipin remodeling. TAZ mutations are associated with several diseases, but studies on the role of TAZ protein in carcinogenesis and radiotherapy (RT) response is lacking. Therefore we investigated the TAZ expression in rectal cancer, and its correlation with RT, clinicopathological and biological variables in the patients participating in a clinical trial of preoperative RT...
2014: PloS One
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