Connexin-43 Mediates Fcγ Receptor-Induced Calcium Signaling by Acting as an NAD/Cyclic ADP-Ribose Transporter.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3853-3853
Author(s):  
Eun-Kyung Song ◽  
Young-Rae Lee ◽  
Hong-Nu Yu ◽  
So-Young Rah ◽  
Uh-Hyun Kim ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Connexin 43 ◽  
Calcium Release ◽  
Catalytic Domain ◽  
Fcγ Receptor ◽  
Murine Macrophages ◽  
Cyclic Adp Ribose ◽  
Intracellular Target ◽  
Intracellular Action ◽  
Insight Into

Abstract Cyclic ADP-ribose (cADPR) is produced from NAD by CD38, a leukocyte receptor and ectoenzyme with its catalytic domain positioned outside of cells, and mobilizes Ca2+ from ryanodine sensitive Ca2+ stores. It has long been questioned how NAD approach CD38 and extracellularly generated cADPR reaches its intracellular target Ca2+ stores. Here we address this question by identifying connexin 43 hemichannels (Cx43) as a transporter of cyclic ADP-ribose as well as NAD in Fcg receptor (FcgR) triggering-induced calcium signaling. FcgR clustering triggers a Ca2+ transient via three sequential steps, Cx43-mediated NAD export, CD38-mediated cADPR production and subsequent Cx43-mediated cADPR import in murine macrophages. FcgR clustering induces Cx43 phosphorylation, thereby opening Cx43 and transporting NAD and cADPR. After cADPR-mediated Ca2+ transient, Cx43 is immediately dephosphorylated and closed, blocking further cADPR transport. This finding is the first evidence showing the involvement of Cx43 in cADPR-mediated Ca2+ release induced by physiological ligand where the apparent topological paradox of extracellular cADPR synthesis and its intracellular action exist. Our results provide new insight into the mechanism of intracellular calcium release triggered by the extracellularly generated calcium mobilizer cADPR, which is involved in (FcgR)-mediated calcium signaling in murine macrophages.

Adenine-based calcium signal pathway messengers: Synthesis and agonistic properties of cyclic ADP-ribose analogs

2008 ◽  
Vol 80 (8) ◽  
pp. 1821-1825
Author(s):  
Liangren Zhang ◽  
Zhenjun Yang ◽  
Andreas H. Guse ◽  
Lihe Zhang
Keyword(s):  
T Lymphocytes ◽  
Calcium Signaling ◽  
Molecular Mechanism ◽  
Calcium Release ◽  
Biological Activities ◽  
Signal Pathway ◽  
Calcium Signal ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Cyclic Adp Ribose

A series of cyclic ADP-ribose (cADPR) analogs, in which modifications mainly focused on riboses, was synthesized in order to explore the molecular mechanism of calcium release regulated by cADPR. Biological activities investigated in intact T-lymphocytes showed that the structurally simplified analogs, N1-ethoxymethyl-substituted cyclic inosine diphosphoribose (cIDPRE), N1,N9-diethoxymethyl-substituted cyclic inosine diphosphoribose (cIDPDE), and N1-ethoxymethyl-substituted cyclic adenosine diphosphoribose (cADPRE) in which the northern ribose or both northern and southern riboses were replaced by ether linkages are membrane-permeant and induce calcium release from intracellular stores. This research has provided novel molecules to probe cADPR-mediated calcium signaling and enlarges our knowledge of the structure-activity relationships of cADPR analogs.

scholarly journals Intercellular calcium signaling via gap junction in connexin-43-transfected cells.

1998 ◽  
Vol 273 (35) ◽  
pp. 22856
Author(s):  
Toshihiko Toyofuku ◽  
Masanori Yabuki ◽  
Kinya Otsu ◽  
Tsunehiko Kuzuya ◽  
Masatsugu Hori ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Gap Junction ◽  
Connexin 43 ◽  
Transfected Cells

Angiotensin II Ca2+ signaling in rat afferent arterioles: stimulation of cyclic ADP ribose and IP3 pathways

2005 ◽  
Vol 288 (4) ◽  
pp. F785-F791 ◽  
Author(s):  
Susan K. Fellner ◽  
William J. Arendshorst
Keyword(s):  
Calcium Release ◽  
Rat Kidney ◽  
Ang Ii ◽  
High Concentration ◽  
Inositol Trisphosphate Receptor ◽  
Cyclic Adp Ribose ◽  
Specific Antagonist ◽  
Afferent Arterioles ◽  
Trisphosphate Receptor ◽  
Calcium Induced Calcium Release

ANG II induces a rise in cytosolic Ca2+ ([Ca2+]i) in vascular smooth muscle (VSM) cells via inositol trisphosphate receptor (IP3R) activation and release of Ca2+ from the sarcoplasmic reticulum (SR). The Ca2+ signal is augmented by calcium-induced calcium release (CICR) and by cyclic adeninediphosphate ribose (cADPR), which sensitizes the ryanodine-sensitive receptor (RyR) to Ca2+ to further amplify CICR. cADPR is synthesized from β-nicotinamide adenine dinucleotide (NAD+) by a membrane-bound bifunctional enzyme, ADPR cyclase. To investigate the possibility that ANG II activates the ADPR cyclase of afferent arterioles, we used inhibitors of the IP3R, RyR, and ADPR cyclase. Afferent arterioles were isolated from rat kidney with the magnetized microsphere and sieving technique and loaded with fura-2 to measure [Ca2+]i. In Ca2+-containing buffer, ANG II increased [Ca2+]i by 125 ± 10 nM. In the presence of the IP3R antagonists TMB-8 and 2-APB, the peak responses to ANG II were reduced by 74 and 81%, respectively. The specific antagonist of cADPR 8-Br ADPR and a high concentration of ryanodine (100 μM) inhibited the ANG II-induced increases in [Ca2+]i by 75 and 69%, respectively. Nicotinamide and Zn2+ are known inhibitors of the VSM ADPR cyclase. Nicotinamide diminished the [Ca2+]i response to ANG II by 66%. In calcium-free buffer, Zn2+ reduced the ANG II response by 68%. Simultaneous blockade of the IP3 and cADPR pathways diminished the [Ca2+]i response to ANG II by 83%. We conclude that ANG II initiates Ca2+ mobilization from the SR in afferent arterioles via the classic IP3R pathway and that ANG II may lead to activation of the ADPR cyclase to form cADPR, which, via its action on the RyR, substantially augments the Ca2+ response.

scholarly journals The Impact of Vitamin D3Supplementation on Mechanisms of Cell Calcium Signaling in Chronic Kidney Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Ingrid Lajdova ◽  
Viera Spustova ◽  
Adrian Oksa ◽  
Zuzana Kaderjakova ◽  
Dusan Chorvat ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Calcium Signaling ◽  
Calcium Homeostasis ◽  
Calcium Release ◽  
Calcium Entry ◽  
Regulatory Mechanisms ◽  
Cell Calcium ◽  
Crac Channels ◽  
The Impact

Intracellular calcium concentration in peripheral blood mononuclear cells (PBMCs) of patients with chronic kidney disease (CKD) is significantly increased, and the regulatory mechanisms maintaining cellular calcium homeostasis are impaired. The purpose of this study was to examine the effect of vitaminD3on predominant regulatory mechanisms of cell calcium homeostasis. The study involved 16 CKD stages 2-3 patients with vitamin D deficiency treated with cholecalciferol 7000–14000 IU/week for 6 months. The regulatory mechanisms of calcium signaling were studied in PBMCs and red blood cells. After vitaminD3supplementation, serum concentration of 25(OH)D3increased (P<0.001) and[Ca2+]idecreased (P<0.001). The differences in[Ca2+]iwere inversely related to differences in 25(OH)D3concentration (P<0.01). VitaminD3supplementation decreased the calcium entry through calcium release activated calcium (CRAC) channels and purinergic P2X7channels. The function of P2X7receptors was changed in comparison with their baseline status, and the expression of these receptors was reduced. There was no effect of vitaminD3on P2X7pores and activity of plasma membrane Ca2+-ATPases. VitaminD3supplementation had a beneficial effect on[Ca2+]idecreasing calcium entry via CRAC and P2X7channels and reducing P2X7receptors expression.

scholarly journals Localization of the Cyclic ADP-ribose-dependent Calcium Signaling Pathway in Hepatocyte Nucleus

2000 ◽  
Vol 275 (32) ◽  
pp. 24807-24817 ◽  
Author(s):  
Keng Meng Khoo ◽  
Myung-Kwan Han ◽  
Jin Bong Park ◽  
Soo Wan Chae ◽  
Uh-Hyun Kim ◽  
...  
Keyword(s):  
Calcium Signaling ◽  
Signaling Pathway ◽  
Hepatocyte Nucleus ◽  
Calcium Signaling Pathway ◽  
Cyclic Adp Ribose

scholarly journals Structure and function of factor XI

Blood ◽  
2010 ◽  
Vol 115 (13) ◽  
pp. 2569-2577 ◽  
Author(s):  
Jonas Emsley ◽  
Paul A. McEwan ◽  
David Gailani
Keyword(s):  
Catalytic Domain ◽  
Structural Features ◽  
Factor Ix ◽  
Missense Mutations ◽  
Factor Xi ◽  
Disk Structure ◽  
Ligand Binding Sites ◽  
And Function ◽  
Insight Into

AbstractFactor XI (FXI) is the zymogen of an enzyme (FXIa) that contributes to hemostasis by activating factor IX. Although bleeding associated with FXI deficiency is relatively mild, there has been resurgence of interest in FXI because of studies indicating it makes contributions to thrombosis and other processes associated with dysregulated coagulation. FXI is an unusual dimeric protease, with structural features that distinguish it from vitamin K–dependent coagulation proteases. The recent availability of crystal structures for zymogen FXI and the FXIa catalytic domain have enhanced our understanding of structure-function relationships for this molecule. FXI contains 4 “apple domains” that form a disk structure with extensive interfaces at the base of the catalytic domain. The characterization of the apple disk structure, and its relationship to the catalytic domain, have provided new insight into the mechanism of FXI activation, the interaction of FXIa with the substrate factor IX, and the binding of FXI to platelets. Analyses of missense mutations associated with FXI deficiency have provided additional clues to localization of ligand-binding sites on the protein surface. Together, these data will facilitate efforts to understand the physiology and pathology of this unusual protease, and development of therapeutics to treat thrombotic disorders.

CD38-Cyclic ADP-Ribose-Mediated Calcium Signaling in Airway Myocytes

2013 ◽  
pp. 247-267
Author(s):  
Deepak A. Deshpande ◽  
Alonso Guedes ◽  
Mythili Dileepan ◽  
Timothy F. Walseth ◽  
Mathur S. Kannan
Keyword(s):  
Calcium Signaling ◽  
Cyclic Adp Ribose
Sign in / Sign up

Export Citation Format

Share Document