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Markus Hoffmann, Stefan Pöhlmann
Influenza A viruses attach to sialic acids on host cells. In this issue of Cell Host & Microbe, Fujioka et al. (2018) show that binding to a specific sialylated cellular protein facilitates infection: engagement of sialic acids linked to the Ca2+ channel CaV 1.2 induces Ca2+ oscillations, which promote infectious entry.
June 13, 2018: Cell Host & Microbe
Makoto Takeda, Takanori Sakaguchi, Takanori Hiraide, Yasushi Shibasaki, Yoshifumi Morita, Hirotoshi Kikuchi, Koji Ikegami, Mitsutoshi Setou, Hiroyuki Konno, Hiroya Takeuchi
The molecular features of hepatocellular carcinoma arising from non-alcoholic fatty liver disease (NAFLD-HCC) are not well known. In this study, we investigated the mechanism by which NAFLD-HCC survives in a fat-rich environment. We found that caveolin (CAV)-1 was overexpressed in clinical specimens from NAFLD-HCC patients. HepG2, HLE, and HuH-7 HCC cell lines showed decreased proliferation in the presence of the saturated fatty acids palmitic acid and stearic acid, although only HLE cells expressed high levels of CAV-1...
June 13, 2018: Cancer Science
Hanan Sayed Mohamed Farghaly, Israa El-Sayed Mohamed Ashry, Mohammad Salem Hareedy
BACKGROUND: Toxic effects of digoxin may occur with normal therapeutic serum level. However, the underlying mechanisms are not fully understood. Nuclear factor kappa-B (NF-kB) is an important transcription factor in most organ systems and is often implicated in the harmful effects of cardiac injury. NF-kB promotes inflammatory responses, mediates adverse cardiac remodeling and has a function correlation with calcium. The voltage-gated L-type calcium channel CaV1.2 mediates the influx of Ca+2 into the cell in response to membrane depolarization...
June 6, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Qingyan Lu, Xuan Luo, Chaoming Mao, Tingting Zheng, Baocui Liu, Xin Dong, Yuepeng Zhou, Chengcheng Xu, Xiao Mou, Fei Wu, Ling Bu, Guoyue Yuan
Hashimoto's thyroiditis (HT) is considered a T helper-type 1 (Th1) cytokine-dominant autoimmune thyroid disease. Caveolin-1 (Cav-1), a part of the thyroxisome multiprotein complex, is localized at the apical pole of thyrocytes and is indispensable for synthesis of thyroid hormones and modulation of oxidative stress in order to avoid cell damage and apoptosis. Reduced autophagy induces thyroid follicular cells (TFC) apoptosis by activating reactive oxygen species (ROS) in HT patients. Nevertheless, whether Cav-1 has roles in the regulation of autophagy remains largely unclear...
June 6, 2018: Endocrine Journal
Vasily Kerov, Joseph G Laird, Mei-Ling Joiner, Sharmon Knecht, Daniel Soh, Jussara Hagen, Sarah H Gardner, Wade Gutierrez, Takeshi Yoshimatsu, Sajag Bhattarai, Teresa Puthussery, Nikolai O Artemyev, Arlene V Drack, Rachel O Wong, Sheila A Baker, Amy Lee
α2 δ-4 is an auxiliary subunit of voltage-gated Cav 1.4 L-type channels that regulate the development and mature exocytotic function of the photoreceptor ribbon synapse. In humans, mutations in the CACNA2D4 gene encoding α2 δ-4 cause heterogeneous forms of vision impairment in humans, the underlying pathogenic mechanisms of which remain unclear. To investigate the retinal function of α2 δ-4, we used genome editing to generate an α2 δ-4 knock-out (α2 δ-4 KO) mouse. In male and female α2 δ-4 KO mice, rod spherules lack ribbons and other synaptic hallmarks early in development...
June 6, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ya-Nan Liang, Yu Liu, Letian Wang, Guodong Yao, Xiaobo Li, Xiangning Meng, Fan Wang, Ming Li, Dandan Tong, Jingshu Geng
Previous studies have indicated that caveolin-1 (Cav-1) is able to bind the signal transduction factor epidermal growth factor receptor (EGFR) to regulate its tyrosine kinase activity. The aim of the present study was to evaluate the clinical significance of Cav-1 gene expression in association with the expression of EGFR in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Cav-1 and EGFR expression using immunohistochemistry, and clinical significance was assessed using multivariate Cox regression analysis, Kaplan-Meier estimator curves and the log-rank test...
June 2018: Oncology Letters
Yoichiro Fujioka, Shinya Nishide, Toyoyuki Ose, Tadaki Suzuki, Izumi Kato, Hideo Fukuhara, Mari Fujioka, Kosui Horiuchi, Aya O Satoh, Prabha Nepal, Sayaka Kashiwagi, Jing Wang, Mika Horiguchi, Yuko Sato, Sarad Paudel, Asuka Nanbo, Tadaaki Miyazaki, Hideki Hasegawa, Katsumi Maenaka, Yusuke Ohba
Influenza A virus (IAV) infection is initiated by the attachment of the viral glycoprotein hemagglutinin (HA) to sialic acid on the host cell surface. However, the sialic acid-containing receptor crucial for IAV infection has remained unidentified. Here, we show that HA binds to the voltage-dependent Ca2+ channel Cav 1.2 to trigger intracellular Ca2+ oscillations and subsequent IAV entry and replication. IAV entry was inhibited by Ca2+ channel blockers (CCBs) or by knockdown of Cav 1.2. The CCB diltiazem also inhibited virus replication in vivo...
May 10, 2018: Cell Host & Microbe
Satoshi Kamijo, Yuichiro Ishii, Shin-Ichiro Horigane, Kanzo Suzuki, Masamichi Ohkura, Junichi Nakai, Hajime Fujii, Sayaka Takemoto-Kimura, Haruhiko Bito
In spite of many association studies linking gene polymorphisms and mutations of L-type Voltage-Gated Ca2+ Channels (VGCC) in neurodevelopmental disorders, such as autism and schizophrenia, specific L-type VGCC roles during brain development remain unclear. Yet, calcium signaling has been shown to be essential for neurodevelopmental processes such as sculpting of neurites, functional wiring and fine tuning of growing networks. To bridge this gap, we performed submembraneous calcium imaging using a membrane-tethered genetically-encoded calcium indicator (GECI) Lck-G-CaMP7...
May 17, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Daohua Jiang, Tamer M Gamal El-Din, Christopher Ing, Peilong Lu, Régis Pomès, Ning Zheng, William A Catterall
Potassium-sensitive hypokalaemic and normokalaemic periodic paralysis are inherited skeletal muscle diseases characterized by episodes of flaccid muscle weakness1,2 . They are caused by single mutations in positively charged residues ('gating charges') in the S4 transmembrane segment of the voltage sensor of the voltage-gated sodium channel Nav 1.4 or the calcium channel Cav 1.11,2 . Mutations of the outermost gating charges (R1 and R2) cause hypokalaemic periodic paralysis1,2 by creating a pathogenic gating pore in the voltage sensor through which cations leak in the resting state3,4 ...
May 16, 2018: Nature
Ying Jiang, Shun Li, Hong Yang, Chunhui Wu, Yiyao Liu
To aggressively proliferate and metastasize, cancer cells are in extreme need of energy supply and nutrients. Therefore, a promising cancer therapy strategy is developed to target its hallmark feature of metabolism. Recent findings revealed the regulatory role of caveolin-1 (Cav-1), a structural protein of caveolae, in cancer metabolism. And low Cav-1 expression in tumor stroma was proved to be a central player of cancer malignant phenotype. Here, we summarized the progressions of studies on Cav-1, mitochondria and cancer metabolism to indicate that the altered metabolism induced by Cav-1 and mitochondria association is a major cause of cancer malignant phenotype...
October 1, 2017: Sheng Wu Yi Xue Gong Cheng Xue za Zhi, Journal of Biomedical Engineering, Shengwu Yixue Gongchengxue Zazhi
Xiaoying Luo, Dan Wang, Xintao Zhu, Guozhen Wang, Yuehua You, Zuowei Ning, Yang Li, Siyi Jin, Yun Huang, Ye Hu, Tingting Chen, Ying Meng, Xu Li
Autophagy, interacting with actin cytoskeleton and the NO-dependent pathway, may affect the phenotype and function of endothelial cells. Moreover, caveolin-1 (Cav-1), as a structure protein in liver sinusoidal endothelial cells (LSECs), is closely related to autophagy. Hence, we aim to explore the role of autophagic degradation of Cav-1 in LSECs defenestration. In vivo, we found the increase of autophagy in liver sinusoidal endothelium in human fibrotic liver. Furthermore, autophagy, degradation of Cav-1, and actin filament (F-actin) remodeling were triggered during the process of CCl4-induced LSECs defenestration; in contrast, autophagy inhibitor 3MA diminished the degradation of Cav-1 to maintain fenestrae and relieve CCl4-induced fibrosis...
May 14, 2018: Cell Death & Disease
Dong-Xia Wang, Yong-Quan Pan, Bing Liu, Li Dai
The objective of the study is to calculate the role and underlying the molecular mechanisms of caveolin-1 (Cav-1) in atherosclerosis (AS). Cav-1 was mainly expressed in the endothelial cells of atherosclerotic lesions in both human patients and apolipoprotein E deficient (ApoE-/- ) mice. Cav-1 deficiency (Cav-1-/- ) attenuated high-fat diet (HFD)-induced atherosclerotic lesions in ApoE-/- mice, supported by the reduced aortic plaques. Cav-1-/- reduced the macrophage content and decreased the release of inflammation-related cytokines or chemokine in serum or abdominal aortas, accompanied with the inactivation of inhibitor κB kinase κ (IKKβ)/p65/IκBα signaling pathway...
May 7, 2018: Biochemical and Biophysical Research Communications
Haijie Yu, Can Yuan, Ruth E Westenbroek, William A Catterall
Stimulation of the L-type Ca2+ current conducted by CaV 1.2 channels in cardiac myocytes by the β-adrenergic/protein kinase A (PKA) signaling pathway requires anchoring of PKA to the CaV 1.2 channel by an A-kinase anchoring protein (AKAP). However, the AKAP(s) responsible for regulation in vivo remain unknown. Here, we test the role of the AKAP Cypher/Zasp in β-adrenergic regulation of CaV 1.2 channels using physiological studies of cardiac ventricular myocytes from young-adult mice lacking the long form of Cypher/Zasp (LCyphKO mice)...
May 9, 2018: Journal of General Physiology
Peter Bartels, Dejie Yu, Hua Huang, Zhenyu Hu, Stefan Herzig, Tuck Wah Soong
The CaV 1.2 L-type calcium channel is a key conduit for Ca2+ influx to initiate excitation-contraction coupling for contraction of the heart and vasoconstriction of the arteries and for altering membrane excitability in neurons. Its α1C pore-forming subunit is known to undergo extensive alternative splicing to produce many CaV 1.2 isoforms that differ in their electrophysiological and pharmacological properties. Here, we examined the structure-function relationship of human CaV 1.2 with respect to the inclusion or exclusion of mutually exclusive exons of the N-terminus exons 1/1a and IS6 segment exons 8/8a...
May 8, 2018: Biophysical Journal
Evan C Rosenberg, Jocelyn J Lippman-Bell, Marcus Handy, Samantha S Soldan, Sanjay Rakhade, Cristina Hilario-Gomez, Kaitlyn Folweiler, Leah Jacobs, Frances E Jensen
Neonatal seizures disrupt normal synaptic maturation and often lead to later-life epilepsy and cognitive deficits. During early life, the brain exhibits heightened synaptic plasticity, in part due to a developmental overabundance of CaV 1.2 L-type voltage gated calcium (Ca2+ ) channels (LT-VGCCs) and Ca2+ -permeable AMPARs (CP-AMPARs) lacking GluA2 subunits. We hypothesized that early-life seizures overactivate these channels, in turn dysregulating Ca2+ -dependent signaling pathways including that of methyl-CPG-binding protein 2 (MeCP2), a transcription factor implicated in the autism spectrum disorder (ASD) Rett Syndrome...
May 5, 2018: Neurobiology of Disease
K Klaus, K Butler, H Gutierrez, S J Durrant, K Pennington
The rs1006737 (A/G) single nucleotide polymorphism within the gene encoding the Cav 1.2 subunit of the L-type voltage-dependent calcium channel (CACNA1C) has been strongly implicated in psychiatric disorders. In addition, calcium channels are sensitive to the effects of glucocorticoids and functional variation may contribute to altered stress responsivity. This study aimed to investigate the role of early life stress (ELS) and its interaction with CACNA1C rs1006737 in affecting the cortisol awakening response (CAR), an indicator of HPA-axis function...
May 4, 2018: Biological Psychology
Evanthia Nanou, William A Catterall
Voltage-gated calcium channels couple depolarization of the cell-surface membrane to entry of calcium, which triggers secretion, contraction, neurotransmission, gene expression, and other physiological responses. They are encoded by ten genes, which generate three voltage-gated calcium channel subfamilies: CaV 1; CaV 2; and CaV 3. At synapses, CaV 2 channels form large signaling complexes in the presynaptic nerve terminal, which are responsible for the calcium entry that triggers neurotransmitter release and short-term presynaptic plasticity...
May 2, 2018: Neuron
Wen Li, Chun Chieh Fan, Tuomo Mäki-Marttunen, Wesley K Thompson, Andrew J Schork, Francesco Bettella, Srdjan Djurovic, Anders M Dale, Ole A Andreassen, Yunpeng Wang
Traditional genome-wide association studies (GWAS) have successfully detected genetic variants associated with schizophrenia. However, only a small fraction of heritability can be explained. Gene-set/pathway-based methods can overcome limitations arising from single nucleotide polymorphism (SNP)-based analysis, but most of them place constraints on size which may exclude highly specific and functional sets, like macromolecules. Voltage-gated calcium (Cav ) channels, belonging to macromolecules, are composed of several subunits whose encoding genes are located far away or even on different chromosomes...
April 28, 2018: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Xiaoyu Deng, Jiali Zhang, Jiazi Su, Hao Liu, Yanlong Cong, Lei Zhang, Kemeng Zhang, Ning Shi, Rongguang Lu, Xijun Yan
The aim of this study was to establish a multiplex PCR (mPCR) method that can simultaneously detect canine parvovirus (CPV-2), canine coronavirus (CCoV) and canine adenovirus (CAV), thereby eliminating the need to detect these pathogens individually. Based on conserved regions in the genomes of these three viruses, the VP2 gene of CPV-2, the endoribonuclease nsp15 gene of CCoV, and the 52K gene of CAV were selected for primer design. The specificity of the mPCR results showed no amplification of canine distemper virus (CDV), canine parainfluenza virus (CPIV), or pseudorabies virus (PRV), indicating that the method had good specificity...
April 19, 2018: Archives of Virology
Yaxiong Yang, Nan Liu, Yuanyuan He, Yuxia Liu, Lin Ge, Linzhi Zou, Sen Song, Wei Xiong, Xiaodong Liu
GCaMP, one popular type of genetically-encoded Ca2+ indicator, has been associated with various side-effects. Here we unveil the intrinsic problem prevailing over different versions and applications, showing that GCaMP containing CaM (calmodulin) interferes with both gating and signaling of L-type calcium channels (CaV 1). GCaMP acts as an impaired apoCaM and Ca2+ /CaM, both critical to CaV 1, which disrupts Ca2+ dynamics and gene expression. We then design and implement GCaMP-X, by incorporating an extra apoCaM-binding motif, effectively protecting CaV 1-dependent excitation-transcription coupling from perturbations...
April 17, 2018: Nature Communications
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