The Role of Calcium in the Stabilization of the NHE1-CHP3 Complex
MULTILEARNING Academy. Zaun, Ph.D H. 03/18/20; 290413; P1
Hans-Christian Zaun, Ph.D
Hans-Christian Zaun, Ph.D
Contributions
Abstract
Hans-Christian Zaun, Ph. D., Scientific Advisor, MultiLearning Group, Montreal, QC, Canada
This poster is adapted for promotional purposes by  Dr. Zaun, on research performed in the laboratory of Dr. John Orlowski, Professor, Department of Physiology, McGill University, Montreal, QC, Canada


Restoration of cardiac intracellular pH (pHi) following acidification is of crucial importance for the maintenance of myocardial contractility. The predominant mechanism responsible for this is the function of the sodium/hydrogen exchanger isoform 1 (NHE1), which is the primary isoform of mammalian myocardium. NHE1 is localized predominantly at the intercalated disks and along the transverse tubular system where it is believed to play an essential role in cardiac pH homeostasis, impulse conductance and excitation-contraction coupling. However, the factors that control the membrane targeting and regulation of NHE1 in heart are poorly understood. Yeast-two hybrid screening identified a cardiac-predominant member of the calcineurin B homologous protein (CHP) family, called CHP3/Tescalcin, that binds directly to the cytoplasmic C-terminal domain of NHE1. However, the functional significance of this interaction has yet to be elucidated. This study undertook biochemical and cellular analysis to determine both the significance of the NHE1-CHP3 complex for pH regulation in cardiac tissue, as well as the significance of calcium-binding in this complex. These studies suggest that CHP3 acts to stabilize the mature form of NHE1 at the plasma membrane, rather than exhibiting a kinetic effect. This results in higher expression of the exchanger at the cellular membrane, accounting for this increase in exchange activity. Furthermore, the binding of Calcium to the CHP3 protein is crucial for the stability of this NHE1-CHP3 complex, suggesting the CHP3 acts as the calcium-myristoyl switch protein.
Hans-Christian Zaun, Ph. D., Scientific Advisor, MultiLearning Group, Montreal, QC, Canada
This poster is adapted for promotional purposes by  Dr. Zaun, on research performed in the laboratory of Dr. John Orlowski, Professor, Department of Physiology, McGill University, Montreal, QC, Canada


Restoration of cardiac intracellular pH (pHi) following acidification is of crucial importance for the maintenance of myocardial contractility. The predominant mechanism responsible for this is the function of the sodium/hydrogen exchanger isoform 1 (NHE1), which is the primary isoform of mammalian myocardium. NHE1 is localized predominantly at the intercalated disks and along the transverse tubular system where it is believed to play an essential role in cardiac pH homeostasis, impulse conductance and excitation-contraction coupling. However, the factors that control the membrane targeting and regulation of NHE1 in heart are poorly understood. Yeast-two hybrid screening identified a cardiac-predominant member of the calcineurin B homologous protein (CHP) family, called CHP3/Tescalcin, that binds directly to the cytoplasmic C-terminal domain of NHE1. However, the functional significance of this interaction has yet to be elucidated. This study undertook biochemical and cellular analysis to determine both the significance of the NHE1-CHP3 complex for pH regulation in cardiac tissue, as well as the significance of calcium-binding in this complex. These studies suggest that CHP3 acts to stabilize the mature form of NHE1 at the plasma membrane, rather than exhibiting a kinetic effect. This results in higher expression of the exchanger at the cellular membrane, accounting for this increase in exchange activity. Furthermore, the binding of Calcium to the CHP3 protein is crucial for the stability of this NHE1-CHP3 complex, suggesting the CHP3 acts as the calcium-myristoyl switch protein.

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies