Shmuel Tuvia - Academia.edu (original) (raw)

Papers by Shmuel Tuvia

Research paper thumbnail of Ubiquitin Ligase Assays and Related Reagents

Research paper thumbnail of Intracoronary delivery of injectable bioabsorbable scaffold (IK-5001) to treat left ventricular remodeling after ST-elevation myocardial infarction: a first-in-man study

Circulation. Cardiovascular interventions, 2014

We aimed to test, for the first time, the feasibility of intracoronary delivery of an innovative,... more We aimed to test, for the first time, the feasibility of intracoronary delivery of an innovative, injectable bioabsorbable scaffold (IK-5001), to prevent or reverse adverse left ventricular remodeling and dysfunction in patients after ST-segment-elevation myocardial infarction. Patients (n=27) with moderate-to-large ST-segment-elevation myocardial infarctions, after successful revascularization, were enrolled. Two milliliters of IK-5001, a solution of 1% sodium alginate plus 0.3% calcium gluconate, was administered by selective injection through the infarct-related coronary artery within 7 days after myocardial infarction. IK-5001 is assumed to permeate the infarcted tissue, cross-linking into a hydrogel and forming a bioabsorbable cardiac scaffold. Coronary angiography, 3 minutes after injection, confirmed that the injection did not impair coronary flow and myocardial perfusion. Furthermore, IK-5001 deployment was not associated with additional myocardial injury or re-elevation of ...

Research paper thumbnail of Local Bending Fluctuations of the Cell Membrane

Biomechanics of Active Movement and Division of Cells, 1994

Research paper thumbnail of The ubiquitin E3 ligase POSH regulates calcium homeostasis through spatial control of Herp

The Journal of Cell Biology, 2007

Research paper thumbnail of Nuclear factor κB in proliferation, activation, and apoptosis in rat hepatic stellate cells

Journal of Hepatology, 2000

BackgrounrVAims: Activation of the transcription factor NFlcB has been demonstrated in activated ... more BackgrounrVAims: Activation of the transcription factor NFlcB has been demonstrated in activated hepatic stellate cells (I-ISCs). We investigated the role of NFKB in proliferation, in activation, and in TNFainduced apoptosis of HSCs. Methods: NFKB activation was inhibited using an adenovirus expressing an IKB dominant negative protein (AdSIrcB) in both quiescent and activated HSCs. Quiescent HSCs were infected with Ad5hB or an adenovirus expressing Bgalactosidase (AdSLacZ). The cells were cultured for 7 days. HSCs activation was determined by cell morphology, smooth muscle a-actin (a-sma) expression, and steady-state mRNA levels of al(I) collagen as assessed by Western blot and RNase protection assay, respectively. Proliferation was determined in culture-activated HSCs by 3H-thymidine incorporation and direct cell counting. Apoptosis was analyzed by infecting quiescent or activated HSCs with AdSIrcB or AdSLacZ, and then treating with TNFa. Apoptosis was demonstrated by I?

Research paper thumbnail of Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding

Genes & Development, 2004

The tumor suppressor gene 101 (tsg101) regulates vesicular trafficking processes in yeast and mam... more The tumor suppressor gene 101 (tsg101) regulates vesicular trafficking processes in yeast and mammals. We report a novel protein, Tal (Tsg101-associated ligase), whose RING finger is necessary for multiple monoubiquitylation of Tsg101. Bivalent binding of Tsg101 to a tandem tetrapeptide motif (PTAP) and to a central region of Tal is essential for Tal-mediated ubiquitylation of Tsg101. By studying endocytosis of the epidermal growth factor receptor and egress of the human immunodeficiency virus, we conclude that Tal regulates a Tsg101-associated complex responsible for the sorting of cargo into cytoplasm-containing vesicles that bud at the multivesicular body and at the plasma membrane.

Research paper thumbnail of Correlation between local cell membrane displacements and filterability of human red blood cells

FEBS Letters, 1992

Local mechanical fluctuations of the cell membrane of human erythrocytes were shown to involve Mg... more Local mechanical fluctuations of the cell membrane of human erythrocytes were shown to involve MgATP-and Mg"+-driven fast membrane displacements. We propose that these local bending deformations of the cell membrane arc important for cell passage through capillaries. In order to verify this hypothesis, we examined cell membrane fluctuations and filterability ol'crythrocy~cs over a wide mngeofmcdium osmolaliries( 180-675 mosmol/kg H20). The results indicate the existence of a positive correlalion between the amplitude of local cell membrane displacements and cell filterability. WC suggest that the occurrence of metabolically driven membrane displacements on the side surface of the red blood cell diminishes its bending stiffness and enables it to fold more efficiently upon entrance into blood capillaries. Thus, local cell membrane displacements seem to play an important role in microcirculation.

Research paper thumbnail of Oxygenation-deoxygenation cycle of erythrocytes modulates submicron cell membrane fluctuations

Biophysical Journal, 1992

Low frequency submicron fluctuations of the cell membrane were recently shown to be characteristi... more Low frequency submicron fluctuations of the cell membrane were recently shown to be characteristic for different cell types, nevertheless their physiological role is yet unknown. Point dark-field microscopy based recordings of these local displacements of cell membrane in human erythrocytes, subjected to cyclic oxygenation and deoxygenation, reveals a reversible decrease of displacement amplitudes from 290 ± 49 to 160 ± 32 nm, respectively. A higher rate of RBC adhesion to a glass substratum is observed upon deoxygenation, probably due to a low level of fluctuation amplitudes. The variation in the amplitude of these displacements were reconstituted in open RBC ghosts by perfusing them with composite solutions of 2,3 diphosphoglycerate, Mg+2, and MgATP, which mimic the intracellular metabolite concentrations in oxygenated and deoxygenated erythrocytes. The mere change in intracellular Mg+2 during oxygenation-deoxygenation cycle is sufficient to explain these findings. The results imply that the magnitude of fluctuations amplitude is directly connected with cell deformability. This study suggests that the physiological cycle of oxygenation-deoxygenation provides a dynamic control of the bending deformability and adhesiveness characteristics of the RBC via a Mg+2-dependent reversible assembly of membrane-skeleton proteins. The existing coupling between oxygenation-deoxygenation of the RBC and its mechanical properties is expected to play a key role in blood microcirculation and may constitute an example of a general situation for other circulating blood cells, where the metabolic control of cytoskeleton dynamics may modulate their dynamic mechanical properties.

Research paper thumbnail of Pharmaceutical Compositions for Delivery of Ferric Iron Compounds, and Methods of Use Thereof

Research paper thumbnail of Pharmaceutical Compositions and Methods of Delvery

Research paper thumbnail of Mechanical Fluctuations of the Membrane-Skeleton Are Dependent on F-Actin ATPase in Human Erythrocytes

The Journal of Cell Biology, Jun 29, 1998

Cell membrane fluctuations (CMF) of human erythrocytes, measured by point dark field microscopy, ... more Cell membrane fluctuations (CMF) of human erythrocytes, measured by point dark field microscopy, were shown to depend, to a large extent, on intracellular MgATP (Levin, S.V., and R. Korenstein. 1991. Biophys. J. 60:733-737). The present study extends that investigation and associates CMF with F-actin's ATPase activity. MgATP was found to reconstitute CMF in red blood cell (RBC) ghosts and RBC skeletons to their levels in intact RBCs, with an apparent K d of 0.29 mM. However, neither non-hydrolyzable ATP ana-logues (AMP-PNP, ATP ␥ S) nor hydrolyzable ones (ITP, GTP), were able to elevate CMF levels. The inhibition of ATPase activity associated with the RBC's skeleton, carried out either by the omission of the MgATP substrate or by the use of several inhibitors (vanadate, phalloidin, and DNase I), resulted in a strong decrease of CMF. We suggest that the actin's ATPase, located at the pointed end of the short actin filament, is responsible for the MgATP stimulation of CMF in RBCs.

Research paper thumbnail of POSH nucleic acids, polypeptides and related methods

Research paper thumbnail of Expression of small heat shock protein αB-crystallin is induced after hepatic stellate cell activation

AJP Gastrointestinal and Liver Physiology

PDF] [Full Text] [Abstract] , December 1, 2004; 82 (2): 534-544. Organ Slice Viability Extended f... more PDF] [Full Text] [Abstract] , December 1, 2004; 82 (2): 534-544. Organ Slice Viability Extended for Pathway Characterization: An in Vitro Model to [PDF] [Full Text] [Abstract] , May 1, 2005; 85 (1): 632-638. Toxicol. Sci. abnormal function of the gastrointestinal tract, hepatobiliary system, and pancreas. It is published 12 times a year (monthly) by the publishes original articles pertaining to all aspects of research involving normal or AJP -Gastrointestinal and Liver Physiology on January 15, 2008 ajpgi.physiology.org Downloaded from

Research paper thumbnail of Abnormal Cardiac Na1 Channel Properties and QT Heart Rate Adaptation in Neonatal AnkyrinB Knockout Mice

The cytoskeleton of the cardiomyocyte has been shown to modulate ion channel function. Cytoskelet... more The cytoskeleton of the cardiomyocyte has been shown to modulate ion channel function. Cytoskeletal disruption in vitro alters Na ϩ channel kinetics, producing a late Na ϩ current that can prolong repolarization. This study describes the properties of the cardiac Na ϩ channel and cardiac repolarization in neonatal mice lacking ankyrin B , a cytoskeletal "adaptor" protein. Using whole-cell voltage clamp techniques, I Na density was lower in ankyrin B (Ϫ/Ϫ) ventricular myocytes than in wild-type (WT) myocytes (Ϫ307Ϯ26 versus Ϫ444Ϯ39 pA/pF, PϽ0.01). Ankyrin B (Ϫ/Ϫ) myocytes exhibited a hyperpolarizing shift in activation and inactivation kinetics compared with WT. Slower recovery from inactivation contributed to the negative shift in steady-state inactivation in ankyrin B (Ϫ/Ϫ). Single Na ϩ channel mean open time was longer in ankyrin B (Ϫ/Ϫ) versus WT at test potentials (V t ) of Ϫ40 mV (1.0Ϯ0.1 versus 0.61Ϯ0.04 ms, PϽ0.05) and Ϫ50 mV (0.8Ϯ0.1 versus 0.39Ϯ0.05 ms, PϽ0.05). Ankyrin B (Ϫ/Ϫ) exhibited late single-channel openings at V t Ϫ40 and Ϫ50 mV, which were not seen in WT. Late I Na contributed to longer action potential durations measured at 90% repolarization (APD 90 ) at 1 Hz stimulation in ankyrin B (Ϫ/Ϫ) compared with WT (354Ϯ26 versus 274Ϯ22 ms, PϽ0.05). From ECG recordings of neonatal mice, heart rates were slower in ankyrin B (Ϫ/Ϫ) than in WT (380Ϯ14 versus 434Ϯ13 bpm, PϽ0.01). Although the QT interval was similar in ankyrin B (Ϫ/Ϫ) and WT at physiological heart rates, QT-interval prolongation in response to heart rate deceleration was greater in ankyrin B (Ϫ/Ϫ). In conclusion, Na ϩ channels in ankyrin B (Ϫ/Ϫ) display reduced I Na density and abnormal kinetics at the whole-cell and single-channel level that contribute to prolonged APD 90 and abnormal QT-rate adaptation.

Research paper thumbnail of Ankyrin-B Is Required for Intracellular Sorting of Structurally Diverse Ca 2 1 Homeostasis Proteins

This report describes a congenital myopathy and major loss of thymic lymphocytes in ankyrin-B ( 2... more This report describes a congenital myopathy and major loss of thymic lymphocytes in ankyrin-B ( 2 / 2 ) mice as well as dramatic alterations in intracellular lo- calization of key components of the Ca 2 1 homeostasis machinery in ankyrin-B ( 2 / 2 ) striated muscle and thy- mus. The sacoplasmic reticulum (SR) and SR/T-tubule junctions are apparently

Research paper thumbnail of beta-Adrenergic agonists regulate cell membrane fluctuations of human erythrocytes

The Journal of Physiology, 1999

Research paper thumbnail of Tyrosine Phosphorylation at a Site Highly Conserved in the L1 Family of Cell Adhesion Molecules Abolishes Ankyrin Binding and Increases Lateral Mobility of Neurofascin

The Journal of Cell Biology, 1997

This paper presents evidence that a member

Research paper thumbnail of Mechanical Fluctuations of the Membrane-Skeleton Are Dependent on F-Actin ATPase in Human Erythrocytes

The Journal of Cell Biology, 1998

Cell membrane fluctuations (CMF) of human erythrocytes, measured by point dark field microscopy, ... more Cell membrane fluctuations (CMF) of human erythrocytes, measured by point dark field microscopy, were shown to depend, to a large extent, on intracellular MgATP (Levin, S.V., and R. Korenstein. 1991. Biophys. J. 60:733-737). The present study extends that investigation and associates CMF with F-actin's ATPase activity. MgATP was found to reconstitute CMF in red blood cell (RBC) ghosts and RBC skeletons to their levels in intact RBCs, with an apparent K d of 0.29 mM. However, neither non-hydrolyzable ATP ana-logues (AMP-PNP, ATP ␥ S) nor hydrolyzable ones (ITP, GTP), were able to elevate CMF levels. The inhibition of ATPase activity associated with the RBC's skeleton, carried out either by the omission of the MgATP substrate or by the use of several inhibitors (vanadate, phalloidin, and DNase I), resulted in a strong decrease of CMF. We suggest that the actin's ATPase, located at the pointed end of the short actin filament, is responsible for the MgATP stimulation of CMF in RBCs.

Research paper thumbnail of Ankyrin-B Is Required for Intracellular Sorting of Structurally Diverse Ca2+ Homeostasis Proteins

The Journal of Cell Biology, 1999

This report describes a congenital myopathy S. Tuvia and M. Buhusi contributed equally to this pa... more This report describes a congenital myopathy S. Tuvia and M. Buhusi contributed equally to this paper.

Research paper thumbnail of The ubiquitin E3 ligase POSH regulates calcium homeostasis through spatial control of Herp

The Journal of Cell Biology, 2007

Research paper thumbnail of Ubiquitin Ligase Assays and Related Reagents

Research paper thumbnail of Intracoronary delivery of injectable bioabsorbable scaffold (IK-5001) to treat left ventricular remodeling after ST-elevation myocardial infarction: a first-in-man study

Circulation. Cardiovascular interventions, 2014

We aimed to test, for the first time, the feasibility of intracoronary delivery of an innovative,... more We aimed to test, for the first time, the feasibility of intracoronary delivery of an innovative, injectable bioabsorbable scaffold (IK-5001), to prevent or reverse adverse left ventricular remodeling and dysfunction in patients after ST-segment-elevation myocardial infarction. Patients (n=27) with moderate-to-large ST-segment-elevation myocardial infarctions, after successful revascularization, were enrolled. Two milliliters of IK-5001, a solution of 1% sodium alginate plus 0.3% calcium gluconate, was administered by selective injection through the infarct-related coronary artery within 7 days after myocardial infarction. IK-5001 is assumed to permeate the infarcted tissue, cross-linking into a hydrogel and forming a bioabsorbable cardiac scaffold. Coronary angiography, 3 minutes after injection, confirmed that the injection did not impair coronary flow and myocardial perfusion. Furthermore, IK-5001 deployment was not associated with additional myocardial injury or re-elevation of ...

Research paper thumbnail of Local Bending Fluctuations of the Cell Membrane

Biomechanics of Active Movement and Division of Cells, 1994

Research paper thumbnail of The ubiquitin E3 ligase POSH regulates calcium homeostasis through spatial control of Herp

The Journal of Cell Biology, 2007

Research paper thumbnail of Nuclear factor κB in proliferation, activation, and apoptosis in rat hepatic stellate cells

Journal of Hepatology, 2000

BackgrounrVAims: Activation of the transcription factor NFlcB has been demonstrated in activated ... more BackgrounrVAims: Activation of the transcription factor NFlcB has been demonstrated in activated hepatic stellate cells (I-ISCs). We investigated the role of NFKB in proliferation, in activation, and in TNFainduced apoptosis of HSCs. Methods: NFKB activation was inhibited using an adenovirus expressing an IKB dominant negative protein (AdSIrcB) in both quiescent and activated HSCs. Quiescent HSCs were infected with Ad5hB or an adenovirus expressing Bgalactosidase (AdSLacZ). The cells were cultured for 7 days. HSCs activation was determined by cell morphology, smooth muscle a-actin (a-sma) expression, and steady-state mRNA levels of al(I) collagen as assessed by Western blot and RNase protection assay, respectively. Proliferation was determined in culture-activated HSCs by 3H-thymidine incorporation and direct cell counting. Apoptosis was analyzed by infecting quiescent or activated HSCs with AdSIrcB or AdSLacZ, and then treating with TNFa. Apoptosis was demonstrated by I?

Research paper thumbnail of Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding

Genes & Development, 2004

The tumor suppressor gene 101 (tsg101) regulates vesicular trafficking processes in yeast and mam... more The tumor suppressor gene 101 (tsg101) regulates vesicular trafficking processes in yeast and mammals. We report a novel protein, Tal (Tsg101-associated ligase), whose RING finger is necessary for multiple monoubiquitylation of Tsg101. Bivalent binding of Tsg101 to a tandem tetrapeptide motif (PTAP) and to a central region of Tal is essential for Tal-mediated ubiquitylation of Tsg101. By studying endocytosis of the epidermal growth factor receptor and egress of the human immunodeficiency virus, we conclude that Tal regulates a Tsg101-associated complex responsible for the sorting of cargo into cytoplasm-containing vesicles that bud at the multivesicular body and at the plasma membrane.

Research paper thumbnail of Correlation between local cell membrane displacements and filterability of human red blood cells

FEBS Letters, 1992

Local mechanical fluctuations of the cell membrane of human erythrocytes were shown to involve Mg... more Local mechanical fluctuations of the cell membrane of human erythrocytes were shown to involve MgATP-and Mg"+-driven fast membrane displacements. We propose that these local bending deformations of the cell membrane arc important for cell passage through capillaries. In order to verify this hypothesis, we examined cell membrane fluctuations and filterability ol'crythrocy~cs over a wide mngeofmcdium osmolaliries( 180-675 mosmol/kg H20). The results indicate the existence of a positive correlalion between the amplitude of local cell membrane displacements and cell filterability. WC suggest that the occurrence of metabolically driven membrane displacements on the side surface of the red blood cell diminishes its bending stiffness and enables it to fold more efficiently upon entrance into blood capillaries. Thus, local cell membrane displacements seem to play an important role in microcirculation.

Research paper thumbnail of Oxygenation-deoxygenation cycle of erythrocytes modulates submicron cell membrane fluctuations

Biophysical Journal, 1992

Low frequency submicron fluctuations of the cell membrane were recently shown to be characteristi... more Low frequency submicron fluctuations of the cell membrane were recently shown to be characteristic for different cell types, nevertheless their physiological role is yet unknown. Point dark-field microscopy based recordings of these local displacements of cell membrane in human erythrocytes, subjected to cyclic oxygenation and deoxygenation, reveals a reversible decrease of displacement amplitudes from 290 ± 49 to 160 ± 32 nm, respectively. A higher rate of RBC adhesion to a glass substratum is observed upon deoxygenation, probably due to a low level of fluctuation amplitudes. The variation in the amplitude of these displacements were reconstituted in open RBC ghosts by perfusing them with composite solutions of 2,3 diphosphoglycerate, Mg+2, and MgATP, which mimic the intracellular metabolite concentrations in oxygenated and deoxygenated erythrocytes. The mere change in intracellular Mg+2 during oxygenation-deoxygenation cycle is sufficient to explain these findings. The results imply that the magnitude of fluctuations amplitude is directly connected with cell deformability. This study suggests that the physiological cycle of oxygenation-deoxygenation provides a dynamic control of the bending deformability and adhesiveness characteristics of the RBC via a Mg+2-dependent reversible assembly of membrane-skeleton proteins. The existing coupling between oxygenation-deoxygenation of the RBC and its mechanical properties is expected to play a key role in blood microcirculation and may constitute an example of a general situation for other circulating blood cells, where the metabolic control of cytoskeleton dynamics may modulate their dynamic mechanical properties.

Research paper thumbnail of Pharmaceutical Compositions for Delivery of Ferric Iron Compounds, and Methods of Use Thereof

Research paper thumbnail of Pharmaceutical Compositions and Methods of Delvery

Research paper thumbnail of Mechanical Fluctuations of the Membrane-Skeleton Are Dependent on F-Actin ATPase in Human Erythrocytes

The Journal of Cell Biology, Jun 29, 1998

Cell membrane fluctuations (CMF) of human erythrocytes, measured by point dark field microscopy, ... more Cell membrane fluctuations (CMF) of human erythrocytes, measured by point dark field microscopy, were shown to depend, to a large extent, on intracellular MgATP (Levin, S.V., and R. Korenstein. 1991. Biophys. J. 60:733-737). The present study extends that investigation and associates CMF with F-actin's ATPase activity. MgATP was found to reconstitute CMF in red blood cell (RBC) ghosts and RBC skeletons to their levels in intact RBCs, with an apparent K d of 0.29 mM. However, neither non-hydrolyzable ATP ana-logues (AMP-PNP, ATP ␥ S) nor hydrolyzable ones (ITP, GTP), were able to elevate CMF levels. The inhibition of ATPase activity associated with the RBC's skeleton, carried out either by the omission of the MgATP substrate or by the use of several inhibitors (vanadate, phalloidin, and DNase I), resulted in a strong decrease of CMF. We suggest that the actin's ATPase, located at the pointed end of the short actin filament, is responsible for the MgATP stimulation of CMF in RBCs.

Research paper thumbnail of POSH nucleic acids, polypeptides and related methods

Research paper thumbnail of Expression of small heat shock protein αB-crystallin is induced after hepatic stellate cell activation

AJP Gastrointestinal and Liver Physiology

PDF] [Full Text] [Abstract] , December 1, 2004; 82 (2): 534-544. Organ Slice Viability Extended f... more PDF] [Full Text] [Abstract] , December 1, 2004; 82 (2): 534-544. Organ Slice Viability Extended for Pathway Characterization: An in Vitro Model to [PDF] [Full Text] [Abstract] , May 1, 2005; 85 (1): 632-638. Toxicol. Sci. abnormal function of the gastrointestinal tract, hepatobiliary system, and pancreas. It is published 12 times a year (monthly) by the publishes original articles pertaining to all aspects of research involving normal or AJP -Gastrointestinal and Liver Physiology on January 15, 2008 ajpgi.physiology.org Downloaded from

Research paper thumbnail of Abnormal Cardiac Na1 Channel Properties and QT Heart Rate Adaptation in Neonatal AnkyrinB Knockout Mice

The cytoskeleton of the cardiomyocyte has been shown to modulate ion channel function. Cytoskelet... more The cytoskeleton of the cardiomyocyte has been shown to modulate ion channel function. Cytoskeletal disruption in vitro alters Na ϩ channel kinetics, producing a late Na ϩ current that can prolong repolarization. This study describes the properties of the cardiac Na ϩ channel and cardiac repolarization in neonatal mice lacking ankyrin B , a cytoskeletal "adaptor" protein. Using whole-cell voltage clamp techniques, I Na density was lower in ankyrin B (Ϫ/Ϫ) ventricular myocytes than in wild-type (WT) myocytes (Ϫ307Ϯ26 versus Ϫ444Ϯ39 pA/pF, PϽ0.01). Ankyrin B (Ϫ/Ϫ) myocytes exhibited a hyperpolarizing shift in activation and inactivation kinetics compared with WT. Slower recovery from inactivation contributed to the negative shift in steady-state inactivation in ankyrin B (Ϫ/Ϫ). Single Na ϩ channel mean open time was longer in ankyrin B (Ϫ/Ϫ) versus WT at test potentials (V t ) of Ϫ40 mV (1.0Ϯ0.1 versus 0.61Ϯ0.04 ms, PϽ0.05) and Ϫ50 mV (0.8Ϯ0.1 versus 0.39Ϯ0.05 ms, PϽ0.05). Ankyrin B (Ϫ/Ϫ) exhibited late single-channel openings at V t Ϫ40 and Ϫ50 mV, which were not seen in WT. Late I Na contributed to longer action potential durations measured at 90% repolarization (APD 90 ) at 1 Hz stimulation in ankyrin B (Ϫ/Ϫ) compared with WT (354Ϯ26 versus 274Ϯ22 ms, PϽ0.05). From ECG recordings of neonatal mice, heart rates were slower in ankyrin B (Ϫ/Ϫ) than in WT (380Ϯ14 versus 434Ϯ13 bpm, PϽ0.01). Although the QT interval was similar in ankyrin B (Ϫ/Ϫ) and WT at physiological heart rates, QT-interval prolongation in response to heart rate deceleration was greater in ankyrin B (Ϫ/Ϫ). In conclusion, Na ϩ channels in ankyrin B (Ϫ/Ϫ) display reduced I Na density and abnormal kinetics at the whole-cell and single-channel level that contribute to prolonged APD 90 and abnormal QT-rate adaptation.

Research paper thumbnail of Ankyrin-B Is Required for Intracellular Sorting of Structurally Diverse Ca 2 1 Homeostasis Proteins

This report describes a congenital myopathy and major loss of thymic lymphocytes in ankyrin-B ( 2... more This report describes a congenital myopathy and major loss of thymic lymphocytes in ankyrin-B ( 2 / 2 ) mice as well as dramatic alterations in intracellular lo- calization of key components of the Ca 2 1 homeostasis machinery in ankyrin-B ( 2 / 2 ) striated muscle and thy- mus. The sacoplasmic reticulum (SR) and SR/T-tubule junctions are apparently

Research paper thumbnail of beta-Adrenergic agonists regulate cell membrane fluctuations of human erythrocytes

The Journal of Physiology, 1999

Research paper thumbnail of Tyrosine Phosphorylation at a Site Highly Conserved in the L1 Family of Cell Adhesion Molecules Abolishes Ankyrin Binding and Increases Lateral Mobility of Neurofascin

The Journal of Cell Biology, 1997

This paper presents evidence that a member

Research paper thumbnail of Mechanical Fluctuations of the Membrane-Skeleton Are Dependent on F-Actin ATPase in Human Erythrocytes

The Journal of Cell Biology, 1998

Cell membrane fluctuations (CMF) of human erythrocytes, measured by point dark field microscopy, ... more Cell membrane fluctuations (CMF) of human erythrocytes, measured by point dark field microscopy, were shown to depend, to a large extent, on intracellular MgATP (Levin, S.V., and R. Korenstein. 1991. Biophys. J. 60:733-737). The present study extends that investigation and associates CMF with F-actin's ATPase activity. MgATP was found to reconstitute CMF in red blood cell (RBC) ghosts and RBC skeletons to their levels in intact RBCs, with an apparent K d of 0.29 mM. However, neither non-hydrolyzable ATP ana-logues (AMP-PNP, ATP ␥ S) nor hydrolyzable ones (ITP, GTP), were able to elevate CMF levels. The inhibition of ATPase activity associated with the RBC's skeleton, carried out either by the omission of the MgATP substrate or by the use of several inhibitors (vanadate, phalloidin, and DNase I), resulted in a strong decrease of CMF. We suggest that the actin's ATPase, located at the pointed end of the short actin filament, is responsible for the MgATP stimulation of CMF in RBCs.

Research paper thumbnail of Ankyrin-B Is Required for Intracellular Sorting of Structurally Diverse Ca2+ Homeostasis Proteins

The Journal of Cell Biology, 1999

This report describes a congenital myopathy S. Tuvia and M. Buhusi contributed equally to this pa... more This report describes a congenital myopathy S. Tuvia and M. Buhusi contributed equally to this paper.

Research paper thumbnail of The ubiquitin E3 ligase POSH regulates calcium homeostasis through spatial control of Herp

The Journal of Cell Biology, 2007