D H MacLennan

Summary

Affiliation: University of Toronto
Country: Canada

Publications

  1. ncbi Ca2+ signalling and muscle disease
    D H MacLennan
    Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
    Eur J Biochem 267:5291-7. 2000
  2. ncbi Sarcolipin overexpression in rat slow twitch muscle inhibits sarcoplasmic reticulum Ca2+ uptake and impairs contractile function
    A Russell Tupling
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
    J Biol Chem 277:44740-6. 2002
  3. ncbi Mechanistic models for muscle diseases and disorders originating in the sarcoplasmic reticulum
    David H MacLennan
    Banting and Best Department of Medical Research, University of Toronto, Charles H Best Institute, 112 College st Toronto, Ontario, Canada MSG 116
    Biochim Biophys Acta 1813:948-64. 2011
  4. ncbi Phospholamban: a crucial regulator of cardiac contractility
    David H MacLennan
    Banting and Best Department of Medical Research, University of Toronto, Charles H Best Institute, 112 College Street, Toronto, Ontario M5G 1L6, Canada
    Nat Rev Mol Cell Biol 4:566-77. 2003
  5. ncbi Scanning mutagenesis reveals a similar pattern of mutation sensitivity in transmembrane sequences M4, M5, and M6, but not in M8, of the Ca2+-ATPase of sarcoplasmic reticulum (SERCA1a)
    W J Rice
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, Toronto, Ontario M5G1L6, Canada
    J Biol Chem 271:31412-9. 1996
  6. ncbi Structure/function analysis of the Ca2+ binding and translocation domain of SERCA1 and the role in Brody disease of the ATP2A1 gene encoding SERCA1
    D H MacLennan
    Banting and Best Department of Medical Research, University of Toronto, Charles H. Best Institute, Ontario, Canada
    Ann N Y Acad Sci 834:175-85. 1997
  7. ncbi The regulation of SERCA-type pumps by phospholamban and sarcolipin
    David H MacLennan
    The Banting and Best Department of Medical Research, University of Toronto, Charles H Best Institute, Ontario, Canada M5G 1L6
    Ann N Y Acad Sci 986:472-80. 2003
  8. ncbi Structure-function relationships in Ca(2+) cycling proteins
    David H MacLennan
    Banting and Best Department of Medical Research, Charles H. Best Institute, University of Toronto, 112 College Street, Toronto, Ontario, Canada M5G 1L6
    J Mol Cell Cardiol 34:897-918. 2002
  9. ncbi Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCA1: absence of structural mutations in five patients with Brody disease
    A Odermatt
    Charles H Best Institute, University of Toronto, 112 College Street, Toronto, Ontario, M5G 1L6, Canada
    Genomics 45:541-53. 1997
  10. ncbi Mutations to Gly2370, Gly2373 or Gly2375 in malignant hyperthermia domain 2 decrease caffeine and cresol sensitivity of the rabbit skeletal-muscle Ca2+-release channel (ryanodine receptor isoform 1)
    G G Du
    Banting and Best Department of Medical Research, University of Toronto, Charles H. Best Institute, 112 College Street, Toronto, Ontario M5G 1L6, Canada
    Biochem J 360:97-105. 2001

Detail Information

Publications82

  1. ncbi Ca2+ signalling and muscle disease
    D H MacLennan
    Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
    Eur J Biochem 267:5291-7. 2000
    ..Overexpression of cardiac calsequestrin leads to cardiomyopathy and ablation of calreticulin alters cardiac development...
  2. ncbi Sarcolipin overexpression in rat slow twitch muscle inhibits sarcoplasmic reticulum Ca2+ uptake and impairs contractile function
    A Russell Tupling
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
    J Biol Chem 277:44740-6. 2002
    ..36 +/- 0.07 versus 6.39 +/- 0.08 pCa units). These results show that NF-SLN expression impairs muscle contractile function by inhibiting SERCA function and diminishing sarcoplasmic reticulum Ca(2+) stores...
  3. ncbi Mechanistic models for muscle diseases and disorders originating in the sarcoplasmic reticulum
    David H MacLennan
    Banting and Best Department of Medical Research, University of Toronto, Charles H Best Institute, 112 College st Toronto, Ontario, Canada MSG 116
    Biochim Biophys Acta 1813:948-64. 2011
    ..This article is part of a Special Issue entitled: 11th European Symposium on Calcium...
  4. ncbi Phospholamban: a crucial regulator of cardiac contractility
    David H MacLennan
    Banting and Best Department of Medical Research, University of Toronto, Charles H Best Institute, 112 College Street, Toronto, Ontario M5G 1L6, Canada
    Nat Rev Mol Cell Biol 4:566-77. 2003
    ..In mice, phospholamban seems to encumber an otherwise healthy heart, but humans with a phospholamban-null genotype develop early-onset dilated cardiomyopathy...
  5. ncbi Scanning mutagenesis reveals a similar pattern of mutation sensitivity in transmembrane sequences M4, M5, and M6, but not in M8, of the Ca2+-ATPase of sarcoplasmic reticulum (SERCA1a)
    W J Rice
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, Toronto, Ontario M5G1L6, Canada
    J Biol Chem 271:31412-9. 1996
    ..Since mutation of M8 failed to identify residues involved in blocking conformational changes or altering Ca2+ affinity, it is apparent that M8 plays a peripheral role in Ca2+ binding and translocation in comparison with M4, M5, and M6...
  6. ncbi Structure/function analysis of the Ca2+ binding and translocation domain of SERCA1 and the role in Brody disease of the ATP2A1 gene encoding SERCA1
    D H MacLennan
    Banting and Best Department of Medical Research, University of Toronto, Charles H. Best Institute, Ontario, Canada
    Ann N Y Acad Sci 834:175-85. 1997
  7. ncbi The regulation of SERCA-type pumps by phospholamban and sarcolipin
    David H MacLennan
    The Banting and Best Department of Medical Research, University of Toronto, Charles H Best Institute, Ontario, Canada M5G 1L6
    Ann N Y Acad Sci 986:472-80. 2003
    ..SLN and PLN appear to bind to the same regulatory site in SERCA. However, in a ternary complex, PLN occupies the regulatory site and SLN binds to the exposed side of PLN and to SERCA...
  8. ncbi Structure-function relationships in Ca(2+) cycling proteins
    David H MacLennan
    Banting and Best Department of Medical Research, Charles H. Best Institute, University of Toronto, 112 College Street, Toronto, Ontario, Canada M5G 1L6
    J Mol Cell Cardiol 34:897-918. 2002
  9. ncbi Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCA1: absence of structural mutations in five patients with Brody disease
    A Odermatt
    Charles H Best Institute, University of Toronto, 112 College Street, Toronto, Ontario, M5G 1L6, Canada
    Genomics 45:541-53. 1997
    ....
  10. ncbi Mutations to Gly2370, Gly2373 or Gly2375 in malignant hyperthermia domain 2 decrease caffeine and cresol sensitivity of the rabbit skeletal-muscle Ca2+-release channel (ryanodine receptor isoform 1)
    G G Du
    Banting and Best Department of Medical Research, University of Toronto, Charles H. Best Institute, 112 College Street, Toronto, Ontario M5G 1L6, Canada
    Biochem J 360:97-105. 2001
    ..Thus amino acids 2163-2458 form a regulatory domain (malignant hyperthermia regulatory domain 2) that regulates caffeine and 4-chloro-m-cresol sensitivity of RyR1...
  11. ncbi A mutation in the human ryanodine receptor gene associated with central core disease
    Y Zhang
    Banting and Best Department of Medical Research, University of Toronto, Charles H Best Institute, Ontario, Canada
    Nat Genet 5:46-50. 1993
    ..This mutation was linked to CCD with a lod score of 4.8 at a recombinant fraction of 0.0 in 16 informative meioses in a 130 member family, suggesting a causal relationship to CCD...
  12. ncbi Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum
    K Otsu
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, Ontario, Canada
    J Biol Chem 265:13472-83. 1990
    ..The two receptors are clearly the products of separate genes, and the gene encoding the cardiac muscle ryanodine receptor was localized to chromosome 1...
  13. ncbi Physical interactions between phospholamban and sarco(endo)plasmic reticulum Ca2+-ATPases are dissociated by elevated Ca2+, but not by phospholamban phosphorylation, vanadate, or thapsigargin, and are enhanced by ATP
    M Asahi
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
    J Biol Chem 275:15034-8. 2000
    ....
  14. ncbi Molecular cloning of cDNA encoding human and rabbit forms of the Ca2+ release channel (ryanodine receptor) of skeletal muscle sarcoplasmic reticulum
    F Zorzato
    Banting and Best Department of Medical Research, University of Toronto, C H Best Institute, Ontario, Canada
    J Biol Chem 265:2244-56. 1990
    ..Several potential calmodulin-binding sites were observed in the sequence, in the region 2800 to 3050...
  15. ncbi A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia
    E F Gillard
    Department of Genetics, Hospital for Sick Children, Ontario, Canada
    Genomics 11:751-5. 1991
    ..This substitution, by analogy to the findings in pig, may be causal for predisposition to MH in this family...
  16. ncbi Molecular cloning and expression of cDNA encoding a lumenal calcium binding glycoprotein from sarcoplasmic reticulum
    E Leberer
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, ON, Canada
    Proc Natl Acad Sci U S A 86:6047-51. 1989
    ..We propose that this lumenal Ca2+ binding glycoprotein of the sarcoplasmic reticulum be designated "sarcalumenin."..
  17. ncbi The structural organization of the human skeletal muscle ryanodine receptor (RYR1) gene
    M S Phillips
    Banting and Best Department of Medical Research, University of Toronto, Charles H Best Institute, 112 College Street, Toronto, Ontario, M5G1L6, Canada
    Genomics 34:24-41. 1996
    ..Knowledge of the structure of the RYR1 gene will provide an invaluable resource for the discovery of mutations in the gene that are causal of human malignant hyperthermia and central core disease...
  18. ncbi Ryanodine receptor gene is a candidate for predisposition to malignant hyperthermia
    D H MacLennan
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, Ontario, Canada
    Nature 343:559-61. 1990
    ..Co-segregation of MH with RYR markers, resulting in a lod score of 4.20 at a linkage distance of zero centimorgans, indicates that MH is likely to be caused by mutations in the RYR gene...
  19. ncbi Characterization of recombinant rabbit cardiac and skeletal muscle Ca2+ release channels (ryanodine receptors) with a novel [3H]ryanodine binding assay
    G G Du
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
    J Biol Chem 273:33259-66. 1998
    ..Analysis of the properties of recombinant RyR2 and RyR1 by measurement of intracellular Fura-2 fluorescence revealed that the different properties of RyR2 and RyR1 are retained in the recombinant expressed proteins...
  20. ncbi Phospholamban domain IB forms an interaction site with the loop between transmembrane helices M6 and M7 of sarco(endo)plasmic reticulum Ca2+ ATPases
    M Asahi
    Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada
    Proc Natl Acad Sci U S A 98:10061-6. 2001
    ..These results suggest that a SERCA1-PLN interaction site occurs between L67 of SERCA1a and domain IB of PLN, which involves SERCA1a D813 and PLN N27 and N30...
  21. ncbi The substitution of Arg for Gly2433 in the human skeletal muscle ryanodine receptor is associated with malignant hyperthermia
    M S Phillips
    Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
    Hum Mol Genet 3:2181-6. 1994
    ..These discrepancies would be consistent with inaccuracies in the CHCT and/or with segregation of a second MH allele within two of the four affected families...
  22. ncbi Positioning of major tryptic fragments in the Ca2+ release channel (ryanodine receptor) resulting from partial digestion of rabbit skeletal muscle sarcoplasmic reticulum
    S R Chen
    Banting and Best Department of Medical Research, University of Toronto, C H Best Institute, Ontario, Canada
    J Biol Chem 268:22642-9. 1993
    ..R., Fleischer, S., and Tempst, P. (1990) J. Biol. Chem. 265, 13143-13149)...
  23. ncbi Chromosome mapping of five human cardiac and skeletal muscle sarcoplasmic reticulum protein genes
    K Otsu
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, Ontario, Canada
    Genomics 17:507-9. 1993
    ..3, and the cardiac calcium release channel gene (RYR2) to the interval between band 1q42.1 (distal) and band 1q43 (proximal)...
  24. ncbi Characterization of cDNA and genomic DNA encoding SERCA1, the Ca(2+)-ATPase of human fast-twitch skeletal muscle sarcoplasmic reticulum, and its elimination as a candidate gene for Brody disease
    Y Zhang
    Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
    Genomics 30:415-24. 1995
    ....
  25. ncbi Mutations in the gene-encoding SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase, are associated with Brody disease
    A Odermatt
    Banting and Best Department of Medical Research, University of Toronto, Charles H Best Institute, Ontario, Canada
    Nat Genet 14:191-4. 1996
    ..essential functional domains and raising the intriguing question: how have these Brody patients partially compensated for the functional knockout of a gene product believed to be essential for fast-twitch skeletal muscle relaxation?..
  26. ncbi Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia
    J Fujii
    Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
    Science 253:448-51. 1991
    ..Assuming that this is the causal mutation for MH, the development of a noninvasive diagnostic test will provide the basis for elimination of the MH gene or its controlled inclusion in swine breeding programs...
  27. ncbi Purification, calcium binding properties, and ultrastructural localization of the 53,000- and 160,000 (sarcalumenin)-dalton glycoproteins of the sarcoplasmic reticulum
    E Leberer
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, Ontario, Canada
    J Biol Chem 265:10118-24. 1990
    ....
  28. ncbi Sarcolipin regulates the activity of SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+-ATPase
    A Odermatt
    Banting and Best Department of Medical Research, University of Toronto, Charles H Best Institute, Toronto, Ontario, Canada M5G 1L6
    J Biol Chem 273:12360-9. 1998
    ..Reduced SLN expression could explain the decrease in SERCA1 activity observed in these muscles and might represent an early functional adaptation to chronic low frequency stimulation...
  29. ncbi Functional characterization of mutants in the predicted pore region of the rabbit cardiac muscle Ca(2+) release channel (ryanodine receptor isoform 2)
    G G Du
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
    J Biol Chem 276:31760-71. 2001
    ....
  30. ncbi Measurement of resting cytosolic Ca2+ concentrations and Ca2+ store size in HEK-293 cells transfected with malignant hyperthermia or central core disease mutant Ca2+ release channels
    J Tong
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
    J Biol Chem 274:693-702. 1999
    ....
  31. ncbi Cosegregation of porcine malignant hyperthermia and a probable causal mutation in the skeletal muscle ryanodine receptor gene in backcross families
    K Otsu
    Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
    Genomics 11:744-50. 1991
    ....
  32. ncbi Rabbit cardiac and slow-twitch muscle express the same phospholamban gene
    J Fujii
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, Canada
    FEBS Lett 227:51-5. 1988
    ..The nucleotide sequences of the 5'- and the very long 3'-untranslated regions of rabbit and dog phospholamban cDNAs also exhibited a high percentage of identity...
  33. ncbi Molecular cloning of the mammalian smooth muscle sarco(endo)plasmic reticulum Ca2+-ATPase
    J Lytton
    Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
    J Biol Chem 264:7059-65. 1989
    ..The expression of the smooth/non-muscle isoform in every tissue tested supports the hypothesis that this molecule represents the "housekeeping" endoplasmic reticulum Ca2+-ATPase...
  34. ncbi Transmembrane helix M6 in sarco(endo)plasmic reticulum Ca(2+)-ATPase forms a functional interaction site with phospholamban. Evidence for physical interactions at other sites
    M Asahi
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
    J Biol Chem 274:32855-62. 1999
    ..Thus, both functional and physical data confirm that PLN interacts with M6 SERCA1a...
  35. ncbi Structure of the rabbit fast-twitch skeletal muscle calsequestrin gene
    A Zarain-Herzberg
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, Ontario, Canada
    J Biol Chem 263:4807-12. 1988
    ....
  36. ncbi Molecular cloning and expression of cDNA encoding the 53,000-dalton glycoprotein of rabbit skeletal muscle sarcoplasmic reticulum
    E Leberer
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, Ontario, Canada
    J Biol Chem 264:3484-93. 1989
    ..The Ca2+ pumping activity of the microsomes isolated from transfected cells was unaltered by the presence of the glycoprotein. Thus the glycoprotein does not appear to modulate Ca2+-ATPase function...
  37. ncbi Refinement of diagnostic assays for a probable causal mutation for porcine and human malignant hyperthermia
    K Otsu
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, Ontario, Canada
    Genomics 13:835-7. 1992
    ..As a result, these PCR-amplified sequences contain constant internal controls for the reliable differentiation by restriction endonuclease digestion of normal, heterozygous, and MH genotypes...
  38. ncbi Fast-twitch and slow-twitch/cardiac Ca2+ ATPase genes map to human chromosomes 16 and 12
    D H MacLennan
    Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
    Somat Cell Mol Genet 13:341-6. 1987
    ..Thus, the two ATPase genes, which are probably related to each other by an ancient duplication event, are not syntenic in the human genome...
  39. ncbi Characterization and localization to human chromosome 1 of human fast-twitch skeletal muscle calsequestrin gene
    J Fujii
    Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
    Somat Cell Mol Genet 16:185-9. 1990
    ..The calsequestrin gene was assigned to human chromosome 1 through the use of a human-mouse somatic cell hybrid mapping panel...
  40. ncbi Structure of the rabbit phospholamban gene, cloning of the human cDNA, and assignment of the gene to human chromosome 6
    J Fujii
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, Ontario, Canada
    J Biol Chem 266:11669-75. 1991
    ..The phospholamban gene was mapped to human chromosome 6, using a human phospholamban cDNA...
  41. ncbi Ryanodine sensitizes the cardiac Ca(2+) release channel (ryanodine receptor isoform 2) to Ca(2+) activation and dissociates as the channel is closed by Ca(2+) depletion
    G G Du
    Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada M5G 1L6
    Proc Natl Acad Sci U S A 98:13625-30. 2001
    ....
  42. ncbi Molecular cloning of cDNAs from human kidney coding for two alternatively spliced products of the cardiac Ca2+-ATPase gene
    J Lytton
    Banting and Best Department of Medical Research, C H Best Institute, University of Toronto, Ontario, Canada
    J Biol Chem 263:15024-31. 1988
    ..The exons which give rise to the alternatively spliced products were located by Southern blotting and sequencing, and the alternative splicing patterns were determined...
  43. ncbi Sarcolipin inhibits polymerization of phospholamban to induce superinhibition of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs)
    Michio Asahi
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
    J Biol Chem 277:26725-8. 2002
    ..Thus the ability of NF-SLN to elevate the content of PLN monomers can account, at least in part, for the superinhibitory effects of NF-SLN in the presence of PLN...
  44. ncbi Identification of Ser38 as the site in cardiac sarcoplasmic reticulum Ca(2+)-ATPase that is phosphorylated by Ca2+/calmodulin-dependent protein kinase
    T Toyofuku
    Banting and Best Department of Medical Research, University of Toronto, C H Best Institute, Ontario, Canada
    J Biol Chem 269:26492-6. 1994
    ..Thus phosphorylation of Ser38 in SERCA2 results in a unique activation of Vmax for Ca2+ transport, providing a potential regulatory mechanism for Ca2+ removal from cardiac and other tissues in which SERCA2 is expressed...
  45. ncbi Cardiac-specific overexpression of sarcolipin in phospholamban null mice impairs myocyte function that is restored by phosphorylation
    Anthony O Gramolini
    Banting and Best Department of Medical Research, Charles H Best Institute, Heart and Stroke Richard Lewar Centre, and Department of Physiology, University of Toronto, Toronto, ON, Canada M5G 1L6
    Proc Natl Acad Sci U S A 103:2446-51. 2006
    ..These data show that overexpression of NF-SLN can inhibit SERCA2a in the absence of PLN and that the inhibition of SERCA2a is correlated with impairment of contractility and calcium cycling in cardiomyocytes...
  46. ncbi Comparative proteomics profiling of a phospholamban mutant mouse model of dilated cardiomyopathy reveals progressive intracellular stress responses
    Anthony O Gramolini
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
    Mol Cell Proteomics 7:519-33. 2008
    ..These results offer a systems-wide perspective of the dynamic maladaptions associated with impaired Ca2+ homeostasis that perturb myocyte function and ultimately converge to cause HF...
  47. ncbi An Ryr1I4895T mutation abolishes Ca2+ release channel function and delays development in homozygous offspring of a mutant mouse line
    Elena Zvaritch
    Banting and Best Department of Medical Research, University of Toronto, Charles H Best Institute, 112 College Street, Toronto, ON, Canada
    Proc Natl Acad Sci U S A 104:18537-42. 2007
    ....
  48. ncbi Interactions of the calcium ATPase with phospholamban and sarcolipin: structure, physiology and pathophysiology
    David H MacLennan
    Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
    J Muscle Res Cell Motil 25:600-1. 2004
  49. ncbi Identification of biochemical adaptations in hyper- or hypocontractile hearts from phospholamban mutant mice by expression proteomics
    Yan Pan
    Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada M5G 1L6
    Proc Natl Acad Sci U S A 101:2241-6. 2004
    ..These data demonstrate that Ca2+ dysregulation, leading to elevated or depressed cardiac contractility, induces compensatory biochemical responses...
  50. ncbi Targeted disruption of the ATP2A1 gene encoding the sarco(endo)plasmic reticulum Ca2+ ATPase isoform 1 (SERCA1) impairs diaphragm function and is lethal in neonatal mice
    Yan Pan
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
    J Biol Chem 278:13367-75. 2003
    ....
  51. ncbi Ca2+ dysregulation in Ryr1(I4895T/wt) mice causes congenital myopathy with progressive formation of minicores, cores, and nemaline rods
    Elena Zvaritch
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, Toronto, Ontario, Canada M5G 1L6
    Proc Natl Acad Sci U S A 106:21813-8. 2009
    ..The IT/+ mouse line is proposed to be a valid model of RyR1-related congenital myopathy, offering high potential for elucidation of the pathogenesis of skeletal muscle disorders arising from impaired EC coupling...
  52. ncbi Constitutively active calcineurin induces cardiac endoplasmic reticulum stress and protects against apoptosis that is mediated by alpha-crystallin-B
    Nicolas Bousette
    Department of Physiology, University of Toronto, Toronto, ON, Canada M5G 1A8
    Proc Natl Acad Sci U S A 107:18481-6. 2010
    ..The identification of Cryab as a downstream effector of calcineurin-induced protection against apoptosis will permit elucidation of its role in cardiac apoptosis and its potential as a therapeutic target...
  53. ncbi Sarcolipin regulates sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) by binding to transmembrane helices alone or in association with phospholamban
    Michio Asahi
    Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada M5G 1L6
    Proc Natl Acad Sci U S A 100:5040-5. 2003
    ..Modeling of the PLN/SLN/SERCA1a complex predicts that the regulator binding cavity in the E(2) conformation of SERCA1a can accommodate both SLN and PLN helices, but not two PLN helices...
  54. ncbi Interaction sites among phospholamban, sarcolipin, and the sarco(endo)plasmic reticulum Ca(2+)-ATPase
    Takashi Morita
    Banting and Best Department of Medical Research, University of Toronto, Charles H Best Institute, 112 College Street, Toronto, Ont, Canada
    Biochem Biophys Res Commun 369:188-94. 2008
    ..These results have led to a revision of our earlier model for the PLN-SLN-SERCA1a complex...
  55. ncbi Polymorphisms and deduced amino acid substitutions in the coding sequence of the ryanodine receptor (RYR1) gene in individuals with malignant hyperthermia
    E F Gillard
    Department of Genetics, Hospital for Sick Children, Toronto, Ontario, Canada
    Genomics 13:1247-54. 1992
    ..The other three polymorphic substitutions failed to segregate with malignant hyperthermia in those families in which they occurred, implying that they represent polymorphisms with little or no effect on the function of the RYR1 gene...
  56. ncbi Bayesian modeling of muscle biopsy contracture testing for malignant hyperthermia susceptibility
    J C Loke
    Department of Anesthesia, Malignant Hyperthermia Investigation Unit, University of Toronto, Ontario, Canada
    Anesthesiology 88:589-600. 1998
    ..Quantifying the limitations inherent in diagnostic testing for MH can help resolve issues in clinical practice, such as the interpretation of a negative test and the apparent lack of complete genetic linkage to RYR1...
  57. ncbi Tbx5-dependent pathway regulating diastolic function in congenital heart disease
    Yonghong Zhu
    Programme in Developmental and Stem Cell Biology, Division of Cardiology and Labatt Family Heart Centre, Programme in Physiology and Experimental Medicine, and Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada
    Proc Natl Acad Sci U S A 105:5519-24. 2008
    ..These results reveal a direct genetic pathway that regulates cardiac diastolic function, implying that patients with structural CHDs may have clinically important underlying anomalies in heart function that merit treatment...
  58. ncbi Sarcolipin retention in the endoplasmic reticulum depends on its C-terminal RSYQY sequence and its interaction with sarco(endo)plasmic Ca(2+)-ATPases
    Anthony O Gramolini
    Banting and Best Department of Medical Research, University of Toronto, Charles H Best Institute, 112 College Street, Toronto, ON, Canada M5G 1L6
    Proc Natl Acad Sci U S A 101:16807-12. 2004
    ..Thus, in the absence of SERCA, retention of NF-SLN in the ER is mediated through its association with other components through the C-terminal RSYQY sequence...
  59. ncbi Analyzing the cardiac muscle proteome by liquid chromatography-mass spectrometry-based expression proteomics
    Anthony O Gramolini
    Banting and Best Department of Medical Research, University of Toronto, Ontario, Canada
    Methods Mol Biol 357:15-31. 2007
    ..The use of gel-free expression proteomics in the detailed analysis of cardiac tissues should yield significant insight into the pathophysiology of these diseases...
  60. ncbi Topology of the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum (RyR1)
    Guo Guang Du
    Banting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada M5G 1L6
    Proc Natl Acad Sci U S A 99:16725-30. 2002
    ..The other three hairpin loops are formed from M5-M6, M7a-M7b, and M8-M10. M9 is not a transmembrane helix, but it might form a selectivity filter between M8 and M10...
  61. ncbi Cardiovascular proteomics: tools to develop novel biomarkers and potential applications
    Sara Arab
    Department of Medicine, University of Toronto, Toronto, Ontario, Canada
    J Am Coll Cardiol 48:1733-41. 2006
    ..The combination of proteomic biomarkers with clinical phenotypes and genetic haplotype information can lead to a more precise diagnosis and therapy on an individual basis--the fundamental premise of "personalized medicine."..
  62. ncbi Multidimensional protein identification technology (MudPIT): technical overview of a profiling method optimized for the comprehensive proteomic investigation of normal and diseased heart tissue
    Thomas Kislinger
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada
    J Am Soc Mass Spectrom 16:1207-20. 2005
    ....
  63. ncbi Cardiac-specific elevations in thyroid hormone enhance contractility and prevent pressure overload-induced cardiac dysfunction
    Maria Giovanna Trivieri
    Heart and Stroke Richard Lewar Centre and Departments of Physiology and Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2
    Proc Natl Acad Sci U S A 103:6043-8. 2006
    ..Our results establish that elevated D2 activity in the heart increases T3 levels and enhances cardiac contractile function while preventing deterioration of cardiac function and altered gene expression after pressure overload...
  64. ncbi Central core disease mutations R4892W, I4897T and G4898E in the ryanodine receptor isoform 1 reduce the Ca2+ sensitivity and amplitude of Ca2+-dependent Ca2+ release
    Guo Guang Du
    Banting and Best Department of Medical Research, Charles H Best Institute, University of Toronto, 112 College St, Toronto, ON, Canada M5G 1L6
    Biochem J 382:557-64. 2004
    ....
  65. ncbi Detection of a novel ryanodine receptor subtype 1 mutation (R328W) in a malignant hyperthermia family by sequencing of a leukocyte transcript
    Julian C P Loke
    Malignant Hyperthermia Investigation Unit, Banting and Best Department of Medical Research, University of Toronto, Canada
    Anesthesiology 99:297-302. 2003
    ..CONCLUSIONS: The feasibility of using complete RYR1 transcripts from leukocytes for sequence analysis offers an efficient and noninvasive method for scanning RYR1 for novel mutations...
  66. ncbi Protocol for the sequence analysis of ryanodine receptor subtype 1 gene transcripts from human leukocytes
    Natasha Kraev
    Department of Anaesthesia, University of Toronto, Ontario, Canada
    Anesthesiology 99:289-96. 2003
    ....
  67. ncbi Proteome dynamics during C2C12 myoblast differentiation
    Thomas Kislinger
    Program in Proteomics and Bioinformatics, University of Toronto, Toronto, Ontario M5S 3E2, Canada
    Mol Cell Proteomics 4:887-901. 2005
    ....
  68. ncbi Crystal structure of type I ryanodine receptor amino-terminal beta-trefoil domain reveals a disease-associated mutation "hot spot" loop
    Fernando J Amador
    Division of Signaling Biology, Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, 101 College Street, Toronto, ON, Canada M5G 1L7
    Proc Natl Acad Sci U S A 106:11040-4. 2009
    ....
  69. ncbi Role of the sequence surrounding predicted transmembrane helix M4 in membrane association and function of the Ca(2+) release channel of skeletal muscle sarcoplasmic reticulum (ryanodine receptor isoform 1)
    Guo Guang Du
    Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario M5G 1L6, Canada
    J Biol Chem 279:37566-74. 2004
    ..Thus, this region may act as a negative regulatory module that increases the energy barrier for Ca(2+) release channel opening...
  70. ncbi A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy
    Kobra Haghighi
    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
    Proc Natl Acad Sci U S A 103:1388-93. 2006
    ..Thus, by chronic suppression of sarcoplasmic reticulum Ca(2+)-ATPase activity, the nonreversible superinhibitory function of mutant PLN-R14Del may lead to inherited dilated cardiomyopathy and premature death in both humans and mice...
  71. ncbi Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility
    Nicole Monnier
    , Inserm U607, Grenoble, France
    Hum Mutat 26:413-25. 2005
    ..This indicates that these patients must be considered as MHS patients with cores, and are clearly differentiated from CCD patients who have been tested positive for MHS...
  72. ncbi Modeling of the inhibitory interaction of phospholamban with the Ca2+ ATPase
    Chikashi Toyoshima
    Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo ku, Tokyo 113 0032, Japan
    Proc Natl Acad Sci U S A 100:467-72. 2003
    ..The model can be extended into the cytoplasmic domain so that Lys-3 in PLN can be cross-linked with Lys-397 and Lys-400 in SERCA1a with little unwinding of the N-terminal helix of PLN...
  73. ncbi Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban
    Joachim P Schmitt
    Department of Genetics, Harvard Medical School and Howard Hughes Medical Institute, 200 Longwood Avenue, Boston, MA 02115, USA
    Science 299:1410-3. 2003
    ..These results indicate that myocellular calcium dysregulation can initiate human heart failure-a finding that may lead to therapeutic opportunities...
  74. ncbi Chronic SR Ca2+-ATPase inhibition causes adaptive changes in cellular Ca2+ transport
    Angela G Brittsan
    Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, 231 Albert Sabin Way, PO Box 670575, Cincinnati, Ohio 45267 0575, USA
    Circ Res 92:769-76. 2003
    ..This ICa modulation may partly compensate for the loss in SERCA2a responsiveness and thereby partially normalize beta-adrenergic inotropy in DM phospholamban mice...
  75. ncbi Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human
    Kobra Haghighi
    Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267, USA
    J Clin Invest 111:869-76. 2003
    ..These findings describe a naturally-occurring loss-of-function human PLN mutation (PLN null). In contrast to reported benefits of PLN ablation in mouse heart failure, humans lacking PLN develop lethal dilated cardiomyopathy...
  76. ncbi Roles of conserved P domain residues and Mg2+ in ATP binding in the ground and Ca2+-activated states of sarcoplasmic reticulum Ca2+-ATPase
    David B McIntosh
    Chemical Pathology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, and National Health Laboratory Service, Groote Schuur Hospital, Cape Town 7925, South Africa
    J Biol Chem 279:32515-23. 2004
    ..Hence, Gly(626) and Asp(703) seem particularly critical for mediating entry into the transition state for phosphoryl transfer upon Ca(2+) binding at the transport sites...
  77. ncbi Cardiac-specific overexpression of sarcolipin inhibits sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2a) activity and impairs cardiac function in mice
    Michio Asahi
    Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    Proc Natl Acad Sci U S A 101:9199-204. 2004
    ..Inhibition of SERCA2a impairs contractility and calcium cycling, but responsiveness to beta-adrenergic agonists may prevent progression to heart failure...
  78. ncbi HSP70 binds to the fast-twitch skeletal muscle sarco(endo)plasmic reticulum Ca2+ -ATPase (SERCA1a) and prevents thermal inactivation
    A Russell Tupling
    Department of Kinesiology, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada
    J Biol Chem 279:52382-9. 2004
    ..These results indicate that HSP70 can bind to SERCA1a and, depending on the severity of heat stress, protect SERCA1a function by stabilizing the nucleotide binding domain...
  79. ncbi Ca2+ signaling in HEK-293 and skeletal muscle cells expressing recombinant ryanodine receptors harboring malignant hyperthermia and central core disease mutations
    Marisa Brini
    Department of Biochemistry and Center for the Study of Biomembranes of the National Research Council CNR, University of Padova, Viale G Colombo 3, 35121 Padova, Italy
    J Biol Chem 280:15380-9. 2005
    ..The results suggest that local Ca(2+) derangements of different degrees account for the specific cellular phenotypes of the two disorders...
  80. ncbi Calcium callisthenics
    N Michael Green
    Nature 418:598-9. 2002
  81. ncbi Probing nucleotide-binding effects on backbone dynamics and folding of the nucleotide-binding domain of the sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase
    Mona Abu-Abed
    Banting and Best Department of Medical Research, University of Toronto, 112 College Street, Toronto, Ontario, Canada M5G 1L6
    Biochem J 379:235-42. 2004
    ....
  82. ncbi Characterization of the ATP-binding domain of the sarco(endo)plasmic reticulum Ca(2+)-ATPase: probing nucleotide binding by multidimensional NMR
    Mona Abu-Abed
    Banting and Best Department of Medical Research, University of Toronto, 112 College Street, Toronto, Ontario, Canada M5G 1L6
    Biochemistry 41:1156-64. 2002
    ..These results are consistent with previous site-directed mutagenesis studies of SERCA1a...