TITLE

Stimulation of Inositol 1,4,5-Trisphosphate (IP3) Receptor Subtypes by Adenophostin A and Its Analogues

AUTHOR(S)
Saleem, Huma; Tovey, Stephen C.; Riley, Andrew M.; Potter, Barry V. L.; Taylor, Colin W.
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Inositol 1,4,5-trisphosphate receptors (IP3R) are intracellular Ca2+ channels. Most animal cells express mixtures of the three IP3R subtypes encoded by vertebrate genomes. Adenophostin A (AdA) is the most potent naturally occurring agonist of IP3R and it shares with IP3 the essential features of all IP3R agonists, namely structures equivalent to the 4,5-bisphosphate and 6-hydroxyl of IP3. The two essential phosphate groups contribute to closure of the clam-like IP3-binding core (IBC), and thereby IP3R activation, by binding to each of its sides (the α- and β-domains). Regulation of the three subtypes of IP3R by AdA and its analogues has not been examined in cells expressing defined homogenous populations of IP3R. We measured Ca2+ release evoked by synthetic adenophostin A (AdA) and its analogues in permeabilized DT40 cells devoid of native IP3R and stably expressing single subtypes of mammalian IP3R. The determinants of high-affinity binding of AdA and its analogues were indistinguishable for each IP3R subtype. The results are consistent with a cation-π interaction between the adenine of AdA and a conserved arginine within the IBC α-domain contributing to closure of the IBC. The two complementary contacts between AdA and the α-domain (cation-π interaction and 3″-phosphate) allow activation of IP3R by an analogue of AdA (3″-dephospho-AdA) that lacks a phosphate group equivalent to the essential 5-phosphate of IP3. These data provide the first structure-activity analyses of key AdA analogues using homogenous populations of all mammalian IP3R subtypes. They demonstrate that differences in the Ca2+ signals evoked by AdA analogues are unlikely to be due to selective regulation of IP3R subtypes.
ACCESSION #
87625743

 

Related Articles

  • Transient Receptor Potential Melastatin 1: A Hair Cell Transduction Channel Candidate. Gerka-Stuyt, John; Au, Adrian; Peachey, Neal S.; Alagramam, Kumar N. // PLoS ONE;Oct2013, Vol. 8 Issue 10, p1 

    Sound and head movements are perceived through sensory hair cells in the inner ear. Mounting evidence indicates that this process is initiated by the opening of mechanically sensitive calcium-permeable channels, also referred to as the mechanoelectrical transducer (MET) channels, reported to be...

  • Expression and Pharmacology of Endogenous Cav Channels in SH-SY5Y Human Neuroblastoma Cells. Sousa, Silmara R.; Vetter, Irina; Ragnarsson, Lotten; Lewis, Richard J. // PLoS ONE;Mar2013, Vol. 8 Issue 3, p1 

    SH-SY5Y human neuroblastoma cells provide a useful in vitro model to study the mechanisms underlying neurotransmission and nociception. These cells are derived from human sympathetic neuronal tissue and thus, express a number of the Cav channel subtypes essential for regulation of important...

  • Cytosolic [Ca2+] regulation of InsP3-evoked puffs. YAMASAKI-MANN, Michiko; DEMURO, Angelo; PARKER, Ian // Biochemical Journal;1/1/2013, Vol. 449 Issue 1, p167 

    InsP3-mediated puffs are fundamental building blocks of cellular Ca2+ signalling, and arise through the concerted opening of clustered InsP3Rs (InsP3 receptors) co-ordinated via Ca2+-induced Ca2+ release. Although the Ca2+ dependency of InsP3Rs has been extensively studied at the single channel...

  • Erratum to: Surface expression and channel function of TRPM8 are cooperatively controlled by transmembrane segments S3 and S4. Kühn, Frank; Winking, Mathis; Kühn, Cornelia; Hoffmann, Daniel; Lückhoff, Andreas // Pflugers Archiv European Journal of Physiology;Nov2013, Vol. 465 Issue 11, p1611 

    No abstract available.

  • Non-Canonical CRL4A/4BCDT2 Interacts with RAD18 to Modulate Post Replication Repair and Cell Survival. Sertic, Sarah; Evolvi, Claudio; Tumini, Emanuela; Plevani, Paolo; Muzi-Falconi, Marco; Rotondo, Giuseppe // PLoS ONE;Mar2013, Vol. 8 Issue 3, p1 

    The Cullin-4CDT2 E3 ubiquitin ligase plays an essential role in DNA replication origin licensing directing degradation of several licensing factors at the G1/S transition in order to prevent DNA re-replication. Recently a RAD18-independent role of Cullin-4CDT2 in PCNA monoubiquitylation has been...

  • Exploring the dominant role of Cav1 channels in signalling to the nucleus. MA, Huan; COHEN, Samuel; LI, Boxing; TSIEN, Richard W. // Bioscience Reports;Feb2013, Vol. 33 Issue 1, p97 

    Calcium is important in controlling nuclear gene expression through the activation of multiple signal-transduction pathways in neurons. Compared with other voltage-gated calcium channels, CaV1 channels demonstrate a considerable advantage in signalling to the nucleus. In this review, we...

  • Triadin regulates cardiac muscle couplon structure and microdomain Ca2+ signalling: a path towards ventricular arrhythmias. Chopra, Nagesh; Knollmann, Björn C. // Cardiovascular Research;May2013, Vol. 98 Issue 2, p187 

    Since the discovery of triadin >20 years ago as one of the major proteins located in the junctional sarcoplasmic reticulum, the field has come a long way in understanding the pivotal role of triadin in orchestrating sarcoplasmic reticulum Ca2+-release and hence excitation–contraction (EC)...

  • Neuronal MHC Class I Expression Is Regulated by Activity Driven Calcium Signaling. Lv, Dan; Shen, Yuqing; Peng, Yaqin; Liu, Jiane; Miao, Fengqin; Zhang, Jianqiong // PLoS ONE;8/11/2015, Vol. 10 Issue 8, p1 

    MHC class I (MHC-I) molecules are important components of the immune system. Recently MHC-I have been reported to also play important roles in brain development and synaptic plasticity. In this study, we examine the molecular mechanism(s) underlying activity-dependent MHC-I expression using...

  • Differential Calcium Signaling by Cone Specific Guanylate Cyclase-Activating Proteins from the Zebrafish Retina. Scholten, Alexander; Koch, Karl-Wilhelm // PLoS ONE;2011, Vol. 6 Issue 8, p1 

    Zebrafish express in their retina a higher number of guanylate cyclase-activating proteins (zGCAPs) than mammalians pointing to more complex guanylate cyclase signaling systems. All six zGCAP isoforms show distinct and partial overlapping expression profiles in rods and cones. We determined...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics