FKBP Binding Characteristics of Cardiac Microsomes from Diverse Vertebrates

Jeyakumar, Loice H.; Ballester, Leomar Y.; Cheng, Dong Sheng; McIntyre, J. Oliver; Chang, Paul; Olivey, Harold E.; Rollins‐Smith, Louise A.; Barnett, Joey V.; Murray, K J; Xiao, Hong; Fleischer, Sidney

doi:10.1006/bbrc.2001.4444

Cited by 108 publications

(94 citation statements)

References 37 publications

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“…FKBP12 and FKBP12.6 (also known as calstabin 1 and 2, respectively) physically interact with all three isoforms of RyR but have different expression levels and binding affinity in different tissues (Chelu et al 2004). FKBP12 copurifies with RyR1 (Jayaraman et al 1992;Brillantes et al 1994) and FKBP12.6 copurifies with RyR2 (Timerman et al 1995;Timerman et al 1996;Barg et al 1997;Jeyakumar et al 2001;Masumiya et al 2003). Although somewhat controversial, a component of the FKBP12 binding site appears to be located between amino acids 2458 and 2468 of RyR1 (Rabbit sequence, SwissProt accession #P11716).…”

Section: Calsequestrinmentioning

confidence: 99%

Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

Lanner¹,

Georgiou²,

Joshi³

et al. 2010

Cold Spring Harbor Perspectives in Biology

677

572

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Ryanodine receptors (RyRs) are located in the sarcoplasmic/endoplasmic reticulum membrane and are responsible for the release of Ca 2þ from intracellular stores during excitation-contraction coupling in both cardiac and skeletal muscle. RyRs are the largest known ion channels (.2MDa) and exist as three mammalian isoforms (RyR 1 -3), all of which are homotetrameric proteins that interact with and are regulated by phosphorylation, redox modifications, and a variety of small proteins and ions. Most RyR channel modulators interact with the large cytoplasmic domain whereas the carboxy-terminal portion of the protein forms the ion-conducting pore. Mutations in RyR2 are associated with human disorders such as catecholaminergic polymorphic ventricular tachycardia whereas mutations in RyR1 underlie diseases such as central core disease and malignant hyperthermia. This chapter examines the current concepts of the structure, function and regulation of RyRs and assesses the current state of understanding of their roles in associated disorders.

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Section: Calsequestrinmentioning

confidence: 99%

Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

Lanner¹,

Georgiou²,

Joshi³

et al. 2010

Cold Spring Harbor Perspectives in Biology

677

572

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“…Microsomal preparations from hearts of various species, including human, exhibit a much larger density of RyRs than IP 3 Rs. For example, RyR densities amounted to ∼3−4 pmol/mg protein in human ventricle [55,56] and to ∼5.5−7 pmol/mg protein in dog, mouse, rabbit and rat ventricle [56]. IP 3 R densities, on the other hand, were ∼0.09 pmol/mg protein in bovine ventricle [16], 0.66 pmol/mg protein in canine ventricle [32], 0.46 pmol/mg protein in ferret ventricle [57] and 0.35 pmol/mg protein in rat ventricle [58].…”

Section: The Dilemma Of Cardiac Ip 3 Receptors: Lost In An Ocean Of Rmentioning

confidence: 99%

Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

Kockskämper

Zima

Roderick

et al. 2008

Journal of Molecular and Cellular Cardiology

172

149

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Inositol 1,4,5-trisphosphate (IP 3 ) is a ubiquitous intracellular messenger regulating diverse functions in almost all mammalian cell types. It is generated by membrane receptors that couple to phospholipase C (PLC), an enzyme which liberates IP 3 from phosphatidylinositol 4,5-bisphosphate (PIP 2 ). The major action of IP 3 , which is hydrophilic and thus translocates from the membrane into the cytoplasm, is to induce Ca 2+ release from endogenous stores through IP 3 receptors (IP 3 Rs). Cardiac excitation-contraction coupling relies largely on ryanodine receptor (RyR)-induced Ca 2+ release from the sarcoplasmic reticulum. Myocytes express a significantly larger number of RyRs compared to IP 3 Rs (∼100:1), and furthermore they experience substantial fluxes of Ca 2+ with each heartbeat. Therefore, the role of IP 3 and IP 3 -mediated Ca 2+ signaling in cardiac myocytes has long been enigmatic. Recent evidence, however, indicates that despite their paucity cardiac IP 3 Rs may play crucial roles in regulating diverse cardiac functions. Strategic localization of IP 3 Rs in cytoplasmic compartments and the nucleus enables them to participate in subsarcolemmal, bulk cytoplasmic and nuclear Ca 2+ signaling in embryonic stem cell-derived and neonatal cardiomyocytes, and in adult cardiac myocytes from the atria and ventricles. Intriguingly, expression of both IP 3 Rs and membrane receptors that couple to PLC/IP 3 signaling is altered in cardiac disease such as atrial fibrillation or heart failure, suggesting the involvement of IP 3 signaling in the pathology of these diseases. Thus, IP 3 exerts important physiological and pathological functions in the heart, ranging from the regulation of pacemaking, excitation-contraction and excitation-transcription coupling to the initiation and/or progression of arrhythmias, hypertrophy and heart failure. KeywordsInositol 1,4,5-trisphosphate; Cardiac myocyte; Calcium; Inotropy; Arrhythmias; Nucleus; Hypertrophy © 2008 Elsevier Inc. All rights reserved. * Corresponding author. E-mail address: jens.kockskaemper@meduni-graz.at (J. Kockskämper).. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript The discovery of IP 3A quarter of a century ago it was shown that D-myo inositol 1,4,5-trisphosphate (IP 3 ) releases Ca 2+ from a non-mitochondrial internal Ca 2+ store [1]. Since this hallmark discovery, IP 3 has emerged as a ubiquitous intracellular messenger, releasing Ca 2+ from stores through activation of IP 3 receptors (IP 3 Rs) in almost all eukaryotic cells. The major IP 3 -sensitive intracellular Ca 2+ store is the endoplasmic reticulum. However, IP 3 has also been shown to release Ca 2+ stored in other compartments, such as the Golgi and the nuclear envelope [2]. In addition, IP 3 Rs are present on the plasma membrane of some cell types, where they can gate Ca 2+ influx [3]. A crucial role for IP 3 -dependent Ca 2+ release has been demonstrated in many mammalian cell types, ranging from tiny platelets, where it initiates blood clottin...

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“…Two isoforms, FKBP12 and FKBP12.6, bind tightly to RyR1 and RyR2, respectively, and may be considered as integral subunits of RyR (30,31). FKBP12 and FKBP12.6 share a high degree of sequence homology (85%), and it has been demonstrated by a site-directed mutagenesis study that three residues specific to FKBP12.6 (Gln-31, Asn-32, and Phe-59) account for the selective binding to cardiac RyR2 (32).…”

mentioning

confidence: 99%

Modeling a Ryanodine Receptor N-terminal Domain Connecting the Central Vestibule and the Corner Clamp Region

Zhu

Zhong

Chen

et al. 2013

Journal of Biological Chemistry

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Background: High resolution structural information only covers 15% of the full-length sequence of RyR. Results: Pseudo-atomic structures are generated for RyR1 fragments 850 -1,056 and RyR2 861-1,067, docked into cryo-EM maps, and supported by FRET experiments. Conclusion: The binding interface between RyR and FKBP consists of electrostatic contacts and contains mutations. Significance: The fragments docked into a domain that forms an intersubunit interaction with a phosphorylation domain.

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FKBP Binding Characteristics of Cardiac Microsomes from Diverse Vertebrates

Cited by 108 publications

References 37 publications

Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

Ryanodine Receptors: Structure, Expression, Molecular Details, and Function in Calcium Release

Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

Modeling a Ryanodine Receptor N-terminal Domain Connecting the Central Vestibule and the Corner Clamp Region

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