Cancer cell behaviors mediated by dysregulated pH dynamics at a glance

Cancer cell behaviors mediated by dysregulated pH dynamics at a glance
Katharine A. White1, Bree K. Grillo-Hill2 and Diane L. Barber1,*

 

ABSTRACT

Dysregulated pH is a common characteristic of cancer cells, as they have an increased intracellular pH (pHi) and a decreased extracellular pH (pHe) compared with normal cells. Recent work has expanded our knowledge of how dysregulated pH dynamics influences cancer cell behaviors, including proliferation, metastasis, metabolic adaptation and tumorigenesis. Emerging data suggest that the dysregulated pH of cancers enables these specific cell behaviors by altering the structure and function of selective pH-sensitive proteins, termed pH sensors. Recent findings also show that, by blocking pHi increases, cancer cell behaviors can be attenuated. This suggests ion transporter inhibition as an effective therapeutic approach, either singly or in combination with targeted therapies. In this Cell Science at a Glance article and accompanying poster, we highlight the interconnected roles of dysregulated pH dynamics in cancer initiation, progression and adaptation.

The Role of Calcium in Inflammation-Associated Bone Resorption

The Role of Calcium in Inflammation-Associated Bone Resorption
Gordon L. Klein
Department of Orthopaedic Surgery and Rehabilitation, University of Texas Medical Branch and Shriners Burns
Hospital, Galveston, TX 77555-0165, USA; gklein@utmb.edu; Tel.: +1-409-747-5700; Fax: +1-409-770-6919
Received: 28 June 2018; Accepted: 27 July 2018; Published: 1 August 2018

 

Abstract:

The aim of this mini-review is to discuss the role of calcium in the process of cytokine-mediated bone resorption in an effort to understand the role circulating calcium may play in the resorption of bone. The liberation of calcium and possibly phosphorus and magnesium by bone resorption may sustain and intensify the inflammatory response. We used a burn injury setting in humans and a burn injury model in animals in order to examine the effects on the bone of the systemic inflammatory response and identified the parathyroid calcium-sensing receptor as the mediator of increasing bone resorption, hence higher interleukin (IL)-1 production, and decreasing bone resorption, hence the lowering of circulating ionized calcium concentration. Thus, extracellular calcium, by means of the parathyroid calcium-sensing receptor, is able to modulate inflammation-mediated resorption.

Viral Membrane Channels: Role and Function in the Virus Life Cycle

Viral Membrane Channels: Role and Function in the Virus Life Cycle
ChingWooen Sze 1 and Yee-Joo Tan 1;2;*
1 Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, MD4, Level 3, 5 Science Drive 2, Singapore 117597, Singapore; E-Mail: micscw@nus.edu.sg
2 Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A * STAR), Singapore 138673, Singapore
* Author to whom correspondence should be addressed; E-Mail: yee_joo_tan@nuhs.edu.sg; Tel.: +65-6516-3692.
Academic Editors: Jose Luis Nieva and Luis Carrasco
Received: 11 April 2015 / Accepted: 12 June 2015 / Published: 23 June 2015

Abstract:

Viroporins are small, hydrophobic trans-membrane viral proteins that oligomerize to form hydrophilic pores in the host cell membranes. These proteins are crucial for the pathogenicity and replication of viruses as they aid in various stages of the viral life cycle, from genome uncoating to viral release. In addition, the ion channel activity of viroporin causes disruption in the cellular ion homeostasis, in particular the calcium ion. Fluctuation in the calcium level triggers the activation of the host defensive programmed cell death pathways as well as the inflammasome, which in turn are being subverted for the viruses’
replication benefits. This review article summarizes recent developments in the functional investigation of viroporins from various viruses and their contributions to viral replication and virulence.

Calcium Channels and Pumps in Viral Infections

Calcium Channels and Pumps in Viral Infections

Xingjuan Chen 1,2, Ruiyuan Cao 2,* and Wu Zhong 2,*
1 Institute of Medical Research, Northwestern Polytechnical University, Xi’an 710072, China; xjchen@nwpu.edu.cn
2 National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China
* Correspondence: 21cc@163.com (R.C.); zhongwu@bmi.ac.cn (W.Z.)

Received: 11 December 2019; Accepted: 24 December 2019; Published: 30 December 2019

 

Abstract:

Ca2+ is essential for virus entry, viral gene replication, virion maturation, and release. The alteration of host cells Ca2+ homeostasis is one of the strategies that viruses use to modulate host cells signal transduction mechanisms in their favor. Host calcium-permeable channels and pumps (including voltage-gated calcium channels, store-operated channels, receptor-operated channels, transient receptor potential ion channels, and Ca2+-ATPase) mediate Ca2+ across the plasma membrane or subcellular organelles, modulating intracellular free Ca2+. Therefore, these Ca2+ channels or pumps present important aspects of viral pathogenesis and virus–host interaction. It has been reported that viruses hijack host calcium channels or pumps, disturbing the cellular homeostatic balance of Ca2+. Such a disturbance benefits virus lifecycles while inducing host cells’ morbidity. Evidence has emerged that pharmacologically targeting the calcium channel or calcium release fromthe endoplasmic reticulum (ER) can obstruct virus lifecycles. Impeding virus-induced abnormal intracellular Ca2+ homeostasis is becoming a useful strategy in the development of potent antiviral drugs. In this present review, the recent identified cellular calcium channels and pumps as targets for virus attack are emphasized.

 

Keywords: virus; calcium channels; calcium pumps; virus–host interaction; antiviral

Viral calciomics: Interplays between Ca2+ and virus

Viral calciomics: Interplays between Ca2+ and virus
Yubin Zhoua, Teryl K. Freyb,*, and Jenny J. Yanga,**
aDepartment of Chemistry, Georgia State University, 50 Decatur St., Atlanta, GA 30303 USA
bDepartment of Biology, Georgia State University, 50 Decatur St., Atlanta, GA 30303 USA

 

Abstract

Ca2+ is one of the most universal and versatile signalling molecules and is involved in almost every aspect of cellular processes. Viruses are adept at utilizing the universal Ca2+ signal to create a tailored cellular environment that meets their own demands. This review summarizes most of the known mechanisms by which viruses perturb Ca2+ homeostasis and utilize Ca2+ and cellular Ca2+- binding proteins to their benefit in their replication cycles. Ca2+ plays important roles in virion structure formation, virus entry, viral gene expression, posttranslational processing of viral proteins and virion maturation and release. As part of the review, we introduce an algorithm to identify linear “EF-hand” Ca2+-binding motifs which resulted in the prediction of a total of 93 previously unrecognized Ca2+-binding motifs in virus proteins. Many of these proteins are nonstructural proteins, a class of proteins among which Ca2+ interactions had not been formerly appreciated. The presence of linear Ca2+-binding motifs in viral proteins enlarges the spectrum of Ca2+–virus interplay and expands the total scenario of viral calciomics.

 

Discovery of Calcium as a Biofilm-Promoting Signal for Vibrio fischeri Reveals New Phenotypes and Underlying Regulatory Complexity

Discovery of Calcium as a Biofilm-Promoting Signal for Vibrio fischeri Reveals New Phenotypes and Underlying Regulatory Complexity
Alice H. TischlerLouise LieCecilia M. ThompsonKaren L. Visick
George O’Toole, Editor

ABSTRACT

Vibrio fischeri uses biofilm formation to promote symbiotic colonization of its squid host, Euprymna scolopes. Control over biofilm formation is exerted at the level of transcription of the symbiosis polysaccharide (syp) locus by a complex set of two-component regulators. Biofilm formation can be induced by overproduction of the sensor kinase RscS, which requires the activities of the hybrid sensor kinase SypF and the response regulator SypG and is negatively regulated by the sensor kinase BinK. Here, we identify calcium as a signal that promotes biofilm formation by biofilm-competent strains under conditions in which biofilms are not typically observed (growth with shaking). This was true for RscS-overproducing cells as well as for strains in which only the negative regulator binK was deleted. The latter results provided, for the first time, an opportunity to induce and evaluate biofilm formation without regulator overexpression. Using these conditions, we determined that calcium induces both syp-dependent and bacterial cellulose synthesis (bcs)-dependent biofilms at the level of transcription of these loci. The calcium-induced biofilms were dependent on SypF, but SypF’s Hpt domain was sufficient for biofilm formation. These data suggested the involvement of another sensor kinase(s) and led to the discovery that both RscS and a previously uncharacterized sensor kinase, HahK, functioned in this pathway. Together, the data presented here reveal both a new signal and biofilm phenotype produced by V. fischeri cells, the coordinate production of two polysaccharides involved in distinct biofilm behaviors, and a new regulator that contributes to control over these processes.

SARS-like cluster of circulating bat coronavirus pose threat for human emergence

SARS-like cluster of circulating bat coronavirus pose threat for human emergence
Vineet D. Menachery1, Boyd L. Yount Jr1, Kari Debbink1,2, Sudhakar Agnihothram3, Lisa E. Gralinski1, Jessica A. Plante1, Rachel L. Graham1, Trevor Scobey1, Xing-Yi Ge8, Eric F. Donaldson1, Scott H. Randell4,5, Antonio Lanzavecchia6, Wayne A. Marasco7, Zhengli-Li Shi8, and Ralph S. Baric1,

 

Abstract
The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. In this study, we examine the disease potential for SARSlike CoVs currently circulating in Chinese horseshoe bat populations. Utilizing the SARS-CoV infectious clone, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild type backbone can efficiently utilize multiple ACE2 receptor orthologs, replicate efficiently in primary human airway cells, and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from CoVs utilizing the novel spike protein. Importantly, based on these findings, we synthetically rederived an infectious full length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Together, the work highlights a continued risk of SARS-CoV reemergence from viruses currently circulating in bat populations.

Emerging corona viruses: Genome structure, replication, and pathogenesis

Emerging corona viruses: Genome structure, replication, and pathogenesis
Yu Chen|Qianyun Liu|Deyin Guo
Key Laboratory of Virology, Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, China  Center for Infection and Immunity Study, School of Medicine, Sun Yat‐sen University, Guangzhou, China

Abstract

The recent emergence of a novel corona virus (2019‐nCoV), which is causing an out break of unusual viral pneumonia in patients in Wuhan, a central city in China, is another warning of the risk of CoVs posed to public health. In this mini review, we provide a brief introduction of the general features of CoVs and describe diseases caused by different CoVs in humans and animals. This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats.


Read Full Article