Messenger (Los Angeles, Calif. : Print)最新文献_第3页

Acidic Ca²⁺ stores in neurodegeneration. 酸性Ca2+储存在神经变性中。

Messenger (Los Angeles, Calif. : Print) Pub Date : 2016-06-01 DOI: 10.1166/msr.2016.1054

Emyr Lloyd-Evans

引用次数: 9

A Special Issue of Messenger 2016. 信使》2016 年特刊。

Messenger (Los Angeles, Calif. : Print) Pub Date : 2016-06-01 DOI: 10.1166/msr.2016.1057

Sandip Patel

引用次数: 0

Calcium Signalling Triggered by NAADP in T Cells Determines Cell Shape and Motility During Immune Synapse Formation. T 细胞中由 NAADP 触发的钙信号决定了免疫突触形成过程中细胞的形状和运动性。

Messenger (Los Angeles, Calif. : Print) Pub Date : 2015-06-01 DOI: 10.1166/msr.2015.1045

Merle Nebel, Bo Zhang, Francesca Odoardi, Alexander Flügel, Barry V L Potter, Andreas H Guse

{"title":"Calcium Signalling Triggered by NAADP in T Cells Determines Cell Shape and Motility During Immune Synapse Formation.","authors":"Merle Nebel, Bo Zhang, Francesca Odoardi, Alexander Flügel, Barry V L Potter, Andreas H Guse","doi":"10.1166/msr.2015.1045","DOIUrl":"10.1166/msr.2015.1045","url":null,"abstract":"Nicotinic acid adenine dinucleotide phosphate (NAADP) has been implicated as an initial Ca2+ trigger in T cell Ca2+ signalling, but its role in formation of the immune synapse in CD4+ effector T cells has not been analysed. CD4+ T cells are activated by the interaction with peptide-MHCII complexes on the surface of antigen-presenting cells. Establishing a two-cell system including primary rat CD4+ T cells specific for myelin basic protein and rat astrocytes enabled us to mirror this activation process in vitro and to analyse Ca2+ signalling, cell shape changes and motility in T cells during formation and maintenance of the immune synapse. After immune synapse formation, T cells showed strong, antigen-dependent increases in free cytosolic calcium concentration ([Ca2+] i ). Analysis of cell shape and motility revealed rounding and immobilization of T cells depending on the amplitude of the Ca2+ signal. NAADP-antagonist BZ194 effectively blocked Ca2+ signals in T cells evoked by the interaction with antigen-presenting astrocytes. BZ194 reduced the percentage of T cells showing high Ca2+ signals thereby supporting the proposed trigger function of NAADP for global Ca2+ signalling. Taken together, the NAADP signalling pathway is further confirmed as a promising target for specific pharmacological intervention to modulate T cell activation.","PeriodicalId":74176,"journal":{"name":"Messenger (Los Angeles, Calif. : Print)","volume":"4 1 1","pages":"104-111"},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64653478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Two-Pore Channels: Lessons from Mutant Mouse Models. 双孔通道:来自突变小鼠模型的经验教训。

Messenger (Los Angeles, Calif. : Print) Pub Date : 2015-06-01 DOI: 10.1166/msr.2015.1041

Margarida Ruas, Antony Galione, John Parrington

{"title":"Two-Pore Channels: Lessons from Mutant Mouse Models.","authors":"Margarida Ruas, Antony Galione, John Parrington","doi":"10.1166/msr.2015.1041","DOIUrl":"https://doi.org/10.1166/msr.2015.1041","url":null,"abstract":"Recent interest in two-pore channels (TPCs) has resulted in a variety of studies dealing with the functional role and mechanism of action of these endo-lysosomal proteins in diverse physiological processes. With the availability of mouse lines harbouring mutant alleles for Tpcnl and/or Tpcn2 genes, several studies have made use of them to validate, consolidate and discover new roles for these channels not only at the cellular level but, importantly, also at the level of the whole organism. The different mutant mouse lines that have been used were derived from distinct genetic manipulation strategies, with the aim of knocking out expression of TPC proteins. However, the expression of different residual TPC sequences predicted to occur in these mutant mouse lines, together with the varied degree to which the effects on Tpcn expression have been studied, makes it important to assess the true knockout status of some of the lines. In this review we summarize these Tpcn mutant mouse lines with regard to their predicted effect on Tpcn expression and the extent to which they have been characterized. Additionally, we discuss how results derived from studies using these Tpcn mutant mouse lines have consolidated previously proposed roles for TPCs, such as mediators of NAADP signalling, endo-lysosomal functions, and pancreatic β cell physiology. We will also review how they have been instrumental in the assignment of new physiological roles for these cation channels in processes such as membrane electrical excitability, neoangiogenesis, viral infection and brown adipose tissue and heart function, revealing, in some cases, a specific contribution of a particular TPC isoform.","PeriodicalId":74176,"journal":{"name":"Messenger (Los Angeles, Calif. : Print)","volume":"4 1","pages":"4-22"},"PeriodicalIF":0.0,"publicationDate":"2015-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1166/msr.2015.1041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10223738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Poring over two-pore channel pore mutants. 研究双孔通道孔隙突变体。

Messenger (Los Angeles, Calif. : Print) Pub Date : 2015-06-01 DOI: 10.1166/msr.2015.1044

Christopher J Penny, Sandip Patel

引用次数: 4

Preferential Coupling of the NAADP Pathway to Exocytosis in T-Cells. T 细胞中 NAADP 通路与外吞作用的优先耦合。

Messenger (Los Angeles, Calif. : Print) Pub Date : 2015-06-01 DOI: 10.1166/msr.2015.1040

Lianne C Davis, Frances M Platt, Antony Galione

引用次数: 0

Design, Synthesis, and Chemical and Biological Properties of Cyclic ADP-4-Thioribose as a Stable Equivalent of Cyclic ADP-Ribose. 环状 ADP-4-Thioribose 作为环状 ADP-Ribose 的稳定等价物的设计、合成及其化学和生物特性。

Messenger (Los Angeles, Calif. : Print) Pub Date : 2014-06-01 DOI: 10.1166/msr.2014.1035

Takayoshi Tsuzuki, Satoshi Takano, Natsumi Sakaguchi, Takashi Kudoh, Takashi Murayama, Takashi Sakurai, Minako Hashii, Haruhiro Higashida, Karin Weber, Andreas H Guse, Tomoshi Kameda, Takatsugu Hirokawa, Yasuhiro Kumaki, Mitsuhiro Arisawa, Barry V L Potter, Satoshi Shuto

{"title":"Design, Synthesis, and Chemical and Biological Properties of Cyclic ADP-4-Thioribose as a Stable Equivalent of Cyclic ADP-Ribose.","authors":"Takayoshi Tsuzuki, Satoshi Takano, Natsumi Sakaguchi, Takashi Kudoh, Takashi Murayama, Takashi Sakurai, Minako Hashii, Haruhiro Higashida, Karin Weber, Andreas H Guse, Tomoshi Kameda, Takatsugu Hirokawa, Yasuhiro Kumaki, Mitsuhiro Arisawa, Barry V L Potter, Satoshi Shuto","doi":"10.1166/msr.2014.1035","DOIUrl":"10.1166/msr.2014.1035","url":null,"abstract":"Here we describe the successful synthesis of cyclic ADP-4-thioribose (cADPtR, 3), designed as a stable mimic of cyclic ADP-ribose (cADPR, 1), a Ca2+-mobilizing second messenger, in which the key N1-β-thioribosyladenosine structure was stereoselectively constructed by condensation between the imidazole nucleoside derivative 8 and the 4-thioribosylamine 7 via equilibrium in 7 between the α-anomer (7α) and the β-anomer (7β) during the reaction course. cADPtR is, unlike cADPR, chemically and biologically stable, while it effectively mobilizes intracellular Ca2+ like cADPR in various biological systems, such as sea urchin homogenate, NG108-15 neuronal cells, and Jurkat T-lymphocytes. Thus, cADPtR is a stable equivalent of cADPR, which can be useful as a biological tool for investigating cADPR-mediated Ca2+-mobilizing pathways.","PeriodicalId":74176,"journal":{"name":"Messenger (Los Angeles, Calif. : Print)","volume":"3 1-2","pages":"35-51"},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869844/pdf/emss-67904.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34502083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cyclic ADP-Ribose and NAADP in Vascular Regulation and Diseases. 环adp核糖和NAADP在血管调节和疾病中的作用。

Messenger (Los Angeles, Calif. : Print) Pub Date : 2013-06-01 DOI: 10.1166/msr.2013.1022

Pin-Lan Li, Yang Zhang, Justine M Abais, Joseph K Ritter, Fan Zhang

{"title":"Cyclic ADP-Ribose and NAADP in Vascular Regulation and Diseases.","authors":"Pin-Lan Li, Yang Zhang, Justine M Abais, Joseph K Ritter, Fan Zhang","doi":"10.1166/msr.2013.1022","DOIUrl":"https://doi.org/10.1166/msr.2013.1022","url":null,"abstract":"Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP), two intracellular Ca2+ mobilizing second messengers, have been recognized as a fundamental signaling mechanism regulating a variety of cell or organ functions in different biological systems. Here we reviewed the literature regarding these ADP-ribosylcyclase products in vascular cells with a major focus on their production, physiological roles, and related underlying mechanisms mediating their actions. In particular, several hot topics in this area of research are comprehensively discussed, which may help understand some of the controversial evidence provided by different studies. For example, some new models are emerging for the agonist receptor coupling of CD38 or ADP-ribosylcyclase and for the formation of an acidic microenvironment to facilitate the production of NAADP in vascular cells. We also summarized the evidence regarding the NAADP-mediated two-phase Ca2+ release with a slow Ca2+-induced Ca2+ release (CICR) and corresponding physiological relevance. The possibility of a permanent structural space between lysosomes and sarcoplasmic reticulum (SR), as well as the critical role of lysosome trafficking in phase 2 Ca2+ release in response to some agonists are also explored. With respect to the molecular targets of NAADP within cells, several possible candidates including SR ryanodine receptors (RyRs), lysosomal transient receptor potential-mucolipin 1 (TRP-ML1) and two pore channels (TPCs) are presented with supporting and opposing evidence. Finally, the possible role of NAADP-mediated regulation of lysosome function in autophagy and atherogenesis is discussed, which may indicate a new direction for further studies on the pathological roles of cADPR and NAADP in the vascular system.","PeriodicalId":74176,"journal":{"name":"Messenger (Los Angeles, Calif. : Print)","volume":"2 2","pages":"63-85"},"PeriodicalIF":0.0,"publicationDate":"2013-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1166/msr.2013.1022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32276229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 21

Questioning regulation of two-pore channels by NAADP. 质疑NAADP对双孔通道的调控作用。

Messenger (Los Angeles, Calif. : Print) Pub Date : 2013-06-01 DOI: 10.1166/msr.2013.1027

Jonathan S Marchant, Sandip Patel

{"title":"Questioning regulation of two-pore channels by NAADP.","authors":"Jonathan S Marchant, Sandip Patel","doi":"10.1166/msr.2013.1027","DOIUrl":"https://doi.org/10.1166/msr.2013.1027","url":null,"abstract":"NAADP is a potent Ca2+ mobilizing messenger [1-3]. Since its discovery in 1995 [4] a considerable volume of literature has shown that NAADP couples cell stimulation to endolysosomal Ca2+ release and thereby the regulation of many cellular functions [5]. However definition of its molecular mechanism of action has proved far from easy. Since 2009, a consensus emerged as several independent groups coalesced upon the two-pore channel (TPC) family as NAADP-activated channels essential for Ca2+ release from endolysosomal Ca2+ stores [6-8]. However this view has been recently challenged by data clearly showing that TPCs function as Na+-selective channels apparently insensitive to NAADP [9;10]. Given the two fundamental characteristics defining an ion channel comprise the opening stimulus and the nature of the permeant ions, scrutiny of these seeming irreconcilable viewpoints is essential. The purpose of this commentary is to distil the remaining consensus while interrogating these divergent viewpoints. From this analysis, critical experimental needs are identified.","PeriodicalId":74176,"journal":{"name":"Messenger (Los Angeles, Calif. : Print)","volume":"2 2","pages":"113-119"},"PeriodicalIF":0.0,"publicationDate":"2013-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1166/msr.2013.1027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32342661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 31

Fibrinogen - a possible extracellular target for inositol phosphates. 纤维蛋白原--肌醇磷酸盐可能的细胞外靶标。

Messenger (Los Angeles, Calif. : Print) Pub Date : 2012-12-01 DOI: 10.1166/msr.2012.1014

Thomas Grint, Andrew M Riley, Stephen J Mills, Barry V L Potter, Stephen T Safrany

{"title":"Fibrinogen - a possible extracellular target for inositol phosphates.","authors":"Thomas Grint, Andrew M Riley, Stephen J Mills, Barry V L Potter, Stephen T Safrany","doi":"10.1166/msr.2012.1014","DOIUrl":"10.1166/msr.2012.1014","url":null,"abstract":"A potential extracellular target for inositol phosphates and analogues with anticancer properties is identified. Proteins from detergent-solubilised HeLa cell lysates bound to a novel affinity column of myo-inositol 1,3,4,5,6-pentakisphosphate (InsP5) coupled to Affigel-10. One high-affinity ligand was fibrinogen Bβ. Inositol phosphates and analogues were able to elute purified fibrinogen from this matrix. InsP5 and the inositol phosphate mimic biphenyl 2,3',4,5',6-pentakisphosphate (BiPhP5) bind fibrinogen in vitro, and block the effects of fibrinogen in A549 cell-based assays of proliferation and migration. They are also able to prevent the fibrinogen-mediated activation of phosphatidylinositol 3-kinase. These effects of fibrinogen appear to be mediated through the intercellular adhesion molecule-1 (ICAM-1), as cells not expressing ICAM-1 fail to respond. In contrast, myo-inositol hexakisphosphate and the epimeric scyllo-inositol 1,2,3,4,5-pentakisphosphate were without effect. These findings are consistent with earlier reports that higher inositol phosphates have anticancer properties. This new mechanism of action and target for these extracellular inositol phosphates to have their effects allows a re-evaluation of earlier data.","PeriodicalId":74176,"journal":{"name":"Messenger (Los Angeles, Calif. : Print)","volume":"1 2","pages":"160-166"},"PeriodicalIF":0.0,"publicationDate":"2012-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988617/pdf/emss-52881.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32276224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0