DAVID GADSBY

Summary

Affiliation: The Rockefeller University
Country: USA

Publications

  1. pmc The ABC protein turned chloride channel whose failure causes cystic fibrosis
    David C Gadsby
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, NY 10021, USA
    Nature 440:477-83. 2006
  2. pmc Ion channels versus ion pumps: the principal difference, in principle
    David C Gadsby
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, 1230 York Avenue, New York, New York 10065 6399, USA
    Nat Rev Mol Cell Biol 10:344-52. 2009
  3. pmc The dynamic relationships between the three events that release individual Na⁺ ions from the Na⁺/K⁺-ATPase
    David C Gadsby
    Marine Biological Laboratory, Woods Hole, Massachusetts 02543, USA
    Nat Commun 3:669. 2012
  4. pmc Review. Peering into an ATPase ion pump with single-channel recordings
    David C Gadsby
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, NY 10065, USA
    Philos Trans R Soc Lond B Biol Sci 364:229-38. 2009
  5. pmc In vivo phosphorylation of CFTR promotes formation of a nucleotide-binding domain heterodimer
    Martin Mense
    Laboratory of Cardiac Membrane Physiology, Rockefeller University, New York, NY 10021, USA
    EMBO J 25:4728-39. 2006
  6. pmc Prolonged nonhydrolytic interaction of nucleotide with CFTR's NH2-terminal nucleotide binding domain and its role in channel gating
    Claudia Basso
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, 1230 York Ave, New York, NY 10021, USA
    J Gen Physiol 122:333-48. 2003
  7. pmc CFTR channel opening by ATP-driven tight dimerization of its nucleotide-binding domains
    Paola Vergani
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, New York 10021, USA
    Nature 433:876-80. 2005
  8. pmc On the mechanism of MgATP-dependent gating of CFTR Cl- channels
    Paola Vergani
    Laboratory of Cardiac Membrane Physiology, Rockefeller University, New York, NY 10021, USA
    J Gen Physiol 121:17-36. 2003
  9. pmc Distinct Mg(2+)-dependent steps rate limit opening and closing of a single CFTR Cl(-) channel
    Athanasios G Dousmanis
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, NY 10021, USA
    J Gen Physiol 119:545-59. 2002
  10. ncbi request reprint Ion channel-like properties of the Na+/K+ Pump
    Pablo Artigas
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, New York 10021, USA
    Ann N Y Acad Sci 976:31-40. 2002

Research Grants

  1. Mechanisms, Structure, and Regulation of CFTR's NBDs
    DAVID GADSBY; Fiscal Year: 2004
  2. NA/K PUMP CURRENT IN ISOLATED HEART CELLS
    DAVID GADSBY; Fiscal Year: 2005
  3. NA/K PUMP CURRENT IN ISOLATED HEART CELLS
    DAVID GADSBY; Fiscal Year: 2007
  4. Mechanisms, Structure, and Regulation of CFTR's NBD's
    DAVID GADSBY; Fiscal Year: 2007
  5. MECHANISMS OF CURRENT MODULATION IN CARDIAC MYOCYTES
    DAVID GADSBY; Fiscal Year: 2007
  6. NA/K PUMP CURRENT IN ISOLATED HEART CELLS
    DAVID GADSBY; Fiscal Year: 2009
  7. Mechanisms, Structure, and Regulation of CFTR's NBD's
    DAVID GADSBY; Fiscal Year: 2009
  8. NA/K PUMP CURRENT IN ISOLATED HEART CELLS
    David C Gadsby; Fiscal Year: 2010
  9. NA/K PUMP CURRENT IN ISOLATED HEART CELLS
    DAVID GADSBY; Fiscal Year: 2009
  10. NA+/K+ PUMP CURRENT IN ISOLATED HEART CELLS
    DAVID GADSBY; Fiscal Year: 2001

Collaborators

Detail Information

Publications22

  1. pmc The ABC protein turned chloride channel whose failure causes cystic fibrosis
    David C Gadsby
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, NY 10021, USA
    Nature 440:477-83. 2006
    ..New structural and biochemical information from prokaryotic ABC proteins and functional information from CFTR channels has led to a unifying mechanism explaining those ATP-driven conformational changes...
  2. pmc Ion channels versus ion pumps: the principal difference, in principle
    David C Gadsby
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, 1230 York Avenue, New York, New York 10065 6399, USA
    Nat Rev Mol Cell Biol 10:344-52. 2009
    ..But new structural and mechanistic information about both of these classes of molecular machines challenges this comfortable separation and forces its re-evaluation...
  3. pmc The dynamic relationships between the three events that release individual Na⁺ ions from the Na⁺/K⁺-ATPase
    David C Gadsby
    Marine Biological Laboratory, Woods Hole, Massachusetts 02543, USA
    Nat Commun 3:669. 2012
    ..The correlations reveal the dynamics of the conformational rearrangements that release three Na(+) to the exterior (or sequester them into their binding sites) one at a time, in an obligatorily sequential manner...
  4. pmc Review. Peering into an ATPase ion pump with single-channel recordings
    David C Gadsby
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, NY 10065, USA
    Philos Trans R Soc Lond B Biol Sci 364:229-38. 2009
    ..Use of variously charged small hydrophilic thiol-specific reagents to probe cysteine targets introduced throughout the pump's transmembrane segments allows mapping and characterization of the route traversed by transported ions...
  5. pmc In vivo phosphorylation of CFTR promotes formation of a nucleotide-binding domain heterodimer
    Martin Mense
    Laboratory of Cardiac Membrane Physiology, Rockefeller University, New York, NY 10021, USA
    EMBO J 25:4728-39. 2006
    ..CFTR phosphorylation by PKA strongly promoted both crosslinking and opening of the split channels, firmly linking head-to-tail NBD1-NBD2 association to channel opening...
  6. pmc Prolonged nonhydrolytic interaction of nucleotide with CFTR's NH2-terminal nucleotide binding domain and its role in channel gating
    Claudia Basso
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, 1230 York Ave, New York, NY 10021, USA
    J Gen Physiol 122:333-48. 2003
    ....
  7. pmc CFTR channel opening by ATP-driven tight dimerization of its nucleotide-binding domains
    Paola Vergani
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, New York 10021, USA
    Nature 433:876-80. 2005
    ..This establishes a molecular mechanism, involving dynamic restructuring of the NBD dimer interface, that is probably common to all members of the ABC protein superfamily...
  8. pmc On the mechanism of MgATP-dependent gating of CFTR Cl- channels
    Paola Vergani
    Laboratory of Cardiac Membrane Physiology, Rockefeller University, New York, NY 10021, USA
    J Gen Physiol 121:17-36. 2003
    ..Based on these and other results, we propose a mechanism linking hydrolytic and gating cycles via ATP-driven dimerization of CFTR's NBDs...
  9. pmc Distinct Mg(2+)-dependent steps rate limit opening and closing of a single CFTR Cl(-) channel
    Athanasios G Dousmanis
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, NY 10021, USA
    J Gen Physiol 119:545-59. 2002
    ..Such stabilization of the open-channel conformation of CFTR by tight binding, or occlusion, of an ATP molecule echoes the stabilization of the active conformation of a G protein by GTP...
  10. ncbi request reprint Ion channel-like properties of the Na+/K+ Pump
    Pablo Artigas
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, New York 10021, USA
    Ann N Y Acad Sci 976:31-40. 2002
    ..These results offer the promise of being able to examine ion occlusion and deocclusion steps at the microscopic level in single Na(+)/K(+) pump molecules...
  11. pmc Large diameter of palytoxin-induced Na/K pump channels and modulation of palytoxin interaction by Na/K pump ligands
    Pablo Artigas
    Laboratory of Cardiac Membrane Physiology, Rockefeller University, New York, NY 10021 6399, USA
    J Gen Physiol 123:357-76. 2004
    ..5 A wide. Enhanced understanding of palytoxin action now allows its use for examining the structures and mechanisms of the gates that occlude/deocclude transported ions during the normal Na/K pump cycle...
  12. pmc Na+/K+-pump ligands modulate gating of palytoxin-induced ion channels
    Pablo Artigas
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, 1230 York Avenue, New York, NY 10021 6399, USA
    Proc Natl Acad Sci U S A 100:501-5. 2003
    ..These findings affirm the alternating-access model of ion pumps and offer the possibility of examining ion occlusion/deocclusion reactions in single pump molecules...
  13. ncbi request reprint Ion occlusion/deocclusion partial reactions in individual palytoxin-modified Na/K pumps
    Pablo Artigas
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, New York 10021, USA
    Ann N Y Acad Sci 986:116-26. 2003
    ..We review that work here and provide evidence that the pore of the PTX-induced pump-channel has a diameter > 6 A...
  14. pmc The ion pathway through the opened Na(+),K(+)-ATPase pump
    Ayako Takeuchi
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, New York 10065, USA
    Nature 456:413-6. 2008
    ....
  15. ncbi request reprint Ion permeation through the Na+,K+-ATPase
    Nicolas Reyes
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, New York 10021, USA
    Nature 443:470-4. 2006
    ..Close structural homology among the catalytic subunits of Ca2+-, Na+,K+- and H+,K+-ATPases argues that their extracytosolic cation exchange pathways all share these physical characteristics...
  16. pmc Ouabain affinity determining residues lie close to the Na/K pump ion pathway
    Pablo Artigas
    Laboratory of Cardiac Membrane Physiology, The Rockefeller University, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 103:12613-8. 2006
    ..The results suggest a method for mapping the footprint of bound cardiotonic steroid on the extracellular surface of the Na/K pump...
  17. pmc Thermodynamics of CFTR channel gating: a spreading conformational change initiates an irreversible gating cycle
    LASZLO CSANADY
    Department of Medical Biochemistry, Semmelweis University, 1088 Budapest, Hungary
    J Gen Physiol 128:523-33. 2006
    ....
  18. pmc Preferential phosphorylation of R-domain Serine 768 dampens activation of CFTR channels by PKA
    LASZLO CSANADY
    Department of Medical Biochemistry, Semmelweis University, Budapest, Germany
    J Gen Physiol 125:171-86. 2005
    ..The observed reduced sensitivity to activation by [PKA] imparted by Ser 768 might serve to ensure activation of WT CFTR by strong stimuli while dampening responses to weak signals...
  19. pmc Functional roles of nonconserved structural segments in CFTR's NH2-terminal nucleotide binding domain
    LASZLO CSANADY
    Department of Medical Biochemistry, Semmelweis University, 1088 Budapest, Hungary
    J Gen Physiol 125:43-55. 2005
    ..In contrast, 633+668 channel function was indistinguishable from WT at both macroscopic and microscopic levels. We conclude that neither nonconserved segment is an essential element of PKA- or nucleotide-dependent regulation...
  20. pmc Sodium flux ratio in Na/K pump-channels opened by palytoxin
    R F Rakowski
    Marine Biological Laboratory, Woods Hole, MA 02543, USA
    J Gen Physiol 130:41-54. 2007
    ....
  21. ncbi request reprint Structural biology: ion pumps made crystal clear
    David C Gadsby
    Nature 450:957-9. 2007
  22. pmc Single ion occupancy and steady-state gating of Na channels in squid giant axon
    Robert F Rakowski
    Marine Biological Laboratory, Woods Hole, Massachusetts 02543, USA
    J Gen Physiol 119:235-49. 2002
    ..55 plus minus 0.03. The composite p(a)p(infinity)1s model describes the steady-state voltage dependence of the persistent TTX-sensitive current well...

Research Grants38

  1. Mechanisms, Structure, and Regulation of CFTR's NBDs
    DAVID GADSBY; Fiscal Year: 2004
    ....
  2. NA/K PUMP CURRENT IN ISOLATED HEART CELLS
    DAVID GADSBY; Fiscal Year: 2005
    ..Explicit kinetic models of the Na/K transport mechanism will be developed to account for experimental observations, and will be refined by fits to the data. ..
  3. NA/K PUMP CURRENT IN ISOLATED HEART CELLS
    DAVID GADSBY; Fiscal Year: 2007
    ....
  4. Mechanisms, Structure, and Regulation of CFTR's NBD's
    DAVID GADSBY; Fiscal Year: 2007
    ..Photolabeling will probe nucleotide interactions with the NBDs. Structural analysis of prokaryotic NBD heterodimers, with an active and a dead catalytic site as in CFTR, will elucidate mechanisms in CFTR's NBDs. ..
  5. MECHANISMS OF CURRENT MODULATION IN CARDIAC MYOCYTES
    DAVID GADSBY; Fiscal Year: 2007
    ..CFTR channels thus offer an opportunity, unprecedented in biology, to examine individual ATP hydrolysis cycles in a single protein molecule, in its natural environment, in real time...
  6. NA/K PUMP CURRENT IN ISOLATED HEART CELLS
    DAVID GADSBY; Fiscal Year: 2009
    ....
  7. Mechanisms, Structure, and Regulation of CFTR's NBD's
    DAVID GADSBY; Fiscal Year: 2009
    ..Photolabeling will probe nucleotide interactions with the NBDs. Structural analysis of prokaryotic NBD heterodimers, with an active and a dead catalytic site as in CFTR, will elucidate mechanisms in CFTR's NBDs. ..
  8. NA/K PUMP CURRENT IN ISOLATED HEART CELLS
    David C Gadsby; Fiscal Year: 2010
    ....
  9. NA/K PUMP CURRENT IN ISOLATED HEART CELLS
    DAVID GADSBY; Fiscal Year: 2009
    ....
  10. NA+/K+ PUMP CURRENT IN ISOLATED HEART CELLS
    DAVID GADSBY; Fiscal Year: 2001
    ....
  11. MECHANISMS, STRUCTURE, AND REGULATION OF CFTR'S NBFS
    DAVID GADSBY; Fiscal Year: 1999
    ..That is what we will measure, for wild-type and mutant channels. ..
  12. NA/K PUMP CURRENT IN ISOLATED HEART CELLS
    DAVID GADSBY; Fiscal Year: 1991
    ....
  13. NA/K PUMP CURRENT IN ISOLATED HEART CELLS
    DAVID GADSBY; Fiscal Year: 1993
    ..We will also begin structure/function studies of exogenous Na/K pumps expressed in Xenopus oocytes from injected mRNA...
  14. Mechanisms, Structure, and Regulation of CFTRs NBDs
    David C Gadsby; Fiscal Year: 2010
    ..Our research aims to understand exactly how a CFTR protein usually works, to help doctors better choose ways to make up the deficit caused by poorly performing CFTR proteins in cystic fibrosis patients. ..