Randy A Hall
Emory University
Project start date: 2008-02-01
Project end date: 2013-01-31
Sponsored Links Excellgen http://Excellgen.com
PDZ SCAFFOLD REGULATION OF ASTROCYTIC GLUTAMATE RECEPTORS AND TRANSPORTERS
Randy A Hall, Associate Professor
Emory University, 1599 Clifton Road, 4th Floor, Atlanta, Ga 30322
Grant 5R01NS055179-03 from National Institute Of Neurological Disorders And Stroke
Keywords: Address; Animal Welfare; Antibodies; Astrocytes; Astrocytus; Astroglia; Bibliography; Binding; Binding (Molecular Function); Brain; Cell Communication and Signaling; Cell Signaling; Central Nervous System; Comment; Comment (PT); Comment [Publication Type]; Commentary; Commentary (PT); Country; Data; Ecological impact; Editorial Comment; Editorial Comment (PT); Electron Microscopy; Encephalon; Encephalons; Environment; Environmental Impact; Equipment; Ethics Committees, Research; Exhibits; Glutamate Receptor; Glutamate Translocase; Glutamate Transport Glycoprotein; Glutamate Transporter; Glutamates; IACUC; IRBs; Impact, Environmental; Institutional Animal Care and Use Committee; Institutional Review Boards; International; Intracellular Communication and Signaling; Knockout Mice; L-Glutamate; Language; Mammals, Mice; Metabotropic Glutamate Receptors; Mice; Mice, Knock-out; Mice, Knockout; Molecular Interaction; Murine; Mus; NHE-RF protein; NHERF; Na+-H+ exchanger-regulatory factor; Nerve Cells; Nerve Transmitter Substances; Nerve Unit; Nervous System, Brain; Nervous System, CNS; Neural Cell; Neuraxis; Neurocyte; Neurons; Neurotransmitters; Null Mouse; Play; Population; Principal Investigator; Programs (PT); Programs [Publication Type]; Proteins; Published Comment; Receptors, Metabotropic Glutamate; Regulation; Research; Research Ethics Committees; Research Resources; Resources; Signal Transduction; Signal Transduction Systems; Signaling; Slice; Sorting - Cell Movement; Synapses; Synaptic; Synaptic Cleft; TXT; Text; Vertebrate Animals; Vertebrates; Viewpoint; Viewpoint (PT); ing; biological signal transduction; experiment; experimental research; experimental study; expiration; gene product; human subject; improved; mGluR3; metabotropic glutamate receptor 3; neuronal; programs; research study; scaffold; scaffolding; sodium-hydrogen exchanger regulatory factor; sorting; vertebrata
Project start date: 2008-02-01
Project end date: 2013-01-31
Budget start date: 1-FEB-2010
Budget end date: 31-JAN-2011
PFA/PA: PA-07-070
5R01NS055179-03 (2010): $302104
Grants awarded to Randy A Hall
MAGI-2 IN BETA-1-ADRENERGIC RECEPTOR FUNCTION
Randy A Hall, Associate Professor
Emory University 1599 Clifton Road, 4th Floor Atlanta, Ga 30322
Grant 5R01GM060982-05 from National Institute Of General Medical Sciences IRG: CDF
Abstract: The beta1-adrenergic receptor (beta1AR) is a G protein-coupled receptor that mediates many of the physiological effects of adrenaline and noradrenaline. Little is known, however, about the molecular mechanisms of beta1AR targeting and regulation in cells. This project aims to study the interaction between the beta1tAR and MAGI-2, a previously-unknown intracellular beta1AR binding partner that associates with the beta1AR carboxyl-terminus via a high-affinity PDZ domain-mediated interaction. The functional significance of the beta1AR/MAGI-2 association is completely unknown. MAGI-2 may be either a scaffolding protein important for subcellular localization of the beta1AR, a regulatory protein that modulates receptor G protein coupling, or a signaling intermediate that couples the beta1AR to diverse intracellular signaling pathways. These possibilities will be explored with a combination of in vitro and cellular experiments. The in vitro experiments will determine the specificity of the beta1AR/MAGI-2 interaction and the potential ability of MAGI-2 to facilitate the formation of complexes between the beta1AR and other proteins. The cellular experiments will focus on the ability of MAGI-2 to regulate the subcellular distribution of the beta1AR and/or to alter beta1AR signaling to effectors such as adenylyl cyclase and MAP kinase. Furthermore, immunostaining of MAGI-2 and beta1AR in primary neuronal cultures and in brain sections will be examined in order to determine how well the two proteins co-localize in native tissues. These studies will provide mechanistic insight into localization and regulation of the beta1AR, a receptor that is a common target for therapeutics used in the treatment of heart disease and other disorders.
Keywords: beta adrenergic receptor, protein structure function, receptor binding, receptor expression, adenylate cyclase, guanosine monophosphate, intracellular transport, mitogen activated protein kinase, other phosphotransferase, protein localization, receptor coupling, histology, immunologic assay /test, laboratory rat
Project start date: 2000-03-01
Project end date: 2005-02-28
5R01GM060982-05 (2004): $212800
5R01GM060982-04 (2003): $212800
5R01GM060982-02 (2001): $214200
1R01GM060982-01 (2000): $234900
NHERF IN BETA-2-ADRENERGIC RECEPTOR SIGNALING
Randy A Hall, Associate Professor
Emory University 1599 Clifton Road, 4th Floor Atlanta, Ga 30322
Grant 5R01HL064713-04 from National Heart, Lung, And Blood Institute IRG: PHRA
Abstract: Stimulation of the beta2-adrenergic receptor (beta2AR) by adrenaline or noradrenaline leads to alterations in the metabolism, excitability, differentiation and growth of many cell types. These effects have traditionally been thought to be mediated exclusively by beta2AR activation of intracellular G proteins. However, it has recently been found that beta2AR regulation of cellular Na+/H+ exchange in some cells involves agonist-promoted coupling of the beta2AR to an intracellular protein called the Na+/H+ exchanger regulatory factor (NHERF). The mechanisms and potential generality of this NHERF-mediated signaling by the beta2AR are unknown. This project aims to elucidate the molecular mechanisms by which the beta2AR can regulate Na+/H+ exchange via association with NHERF, and also aims to find out whether the beta2AR can regulate physiological processes other than Na+/H+ exchange in a NHERF-mediated fashion. Since NHERF seems to act as either an allosteric regulatory protein or adaptor protein, the ability of the beta2AR to regulate the set of intracellular proteins bound by NHERF will be examined. The ability of the beta2AR to regulate the activity of another NHERF binding partner, the platelet-derived growth factor receptor, will also be studied, as will the capacity of NHERF to alter cell growth and proliferation in a beta2AR-regulated fashion. The phosphorylation of NHERF by G protein-coupled receptor kinase 6A, and possibly by other kinases, will also be examined, since an understanding of the regulation of NHERF by phosphorylation may be required for an understanding of NHERF-mediated signaling by the beta2AR. These studies will provide insight into hovel signaling pathways activated by the beta2AR, a receptor that is a common target for therapeutics used in the treatment of hypertension, heart disease and other disorders.
Keywords: beta adrenergic receptor, cell growth regulation, membrane transport protein, receptor expression, G protein coupled receptor kinase, cardiovascular pharmacology, cell proliferation, growth factor receptor, hydrogen ion, phosphorylation, platelet derived growth factor, receptor binding, sodium hydrogen exchanger, sodium ion, immunoprecipitation, protein purification, radiotracer, tissue /cell culture, western blotting
Project start date: 2000-04-10
Project end date: 2004-03-31
5R01HL064713-04 (2003): $267750
5R01HL064713-02 (2001): $267750
1R01HL064713-01 (2000): $293115
Direct Interaction Between GABA-A And GABA-B Receptors
Randy A Hall, Associate Professor
Emory University 1599 Clifton Road, 4th Floor Atlanta, Ga 30322
Grant 1R01NS045644-01 from National Institute Of Neurological Disorders And Stroke IRG: MDCN
Abstract: Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian brain. GABA exerts its physiological actions in the brain via the activation of two distinct types of receptor GABA-A receptors, which are ligand-gated ion channels, and GABA-B receptors, which are G proteincoupled receptors. GABA-A and GABA-B receptors are known to exhibit forms of cross-talk and mutual regulation for which no mechanism has been defined. This project aims to study the importance of a novel and direct interaction found between the GABA-BR1 receptor and the gamma2 subunit of the GABA-A receptor. This physical association may provide a mechanism to allow for direct cross-talk between GABA-A and GABA-B receptors. The structural determinants and physiological significance of this interaction, however, are completely unknown at the present time. The specific regions of GABA-BR1 and the gamma2 subunit of the GABA-A receptor involved in mediating their interaction will be elucidated using a mutagenesis approach in combination with both co-immunoprecipitation and fusion protein pull-down studies. The effects of GABA-A receptor association on GABA-B receptor pharmacology will be studied in ligand binding assays, and GABA-A receptor modulation of GABA-B receptor signaling and internalization will also be analyzed. Furthermore, GABA-B receptor regulation of GABA-A receptor pharmacology, channel activity and phosphorylation will be examined, with an emphasis on determining the functional importance of the direct interaction between GABA-BR1 and the GABA-A receptor gamma2 subunit. These studies will shed new light on the regulation of cellular responses to GABA and the molecular basis for cross-talk between GABA-A and GABA-B receptors. Such information is critical for a comprehensive understanding of pharmaceuticals acting on GABA receptors. GABA-A receptors are the targets for such commonly prescribed therapeutic drugs as benzodiazepines and barbiturates, while the more recently-identified GABA-B receptors represent excellent potential targets for novel therapeutic drugs aimed at treating disorders such as schizophrenia, epilepsy, anxiety, chronic pain and depression.
Keywords: GABA receptor, brain, gamma aminobutyrate, protein protein interaction, G protein, biological signal transduction, membrane channel, neurotransmitter, phosphorylation, receptor binding, receptor expression, SDS polyacrylamide gel electrophoresis, cell line, confocal scanning microscopy, immunoprecipitation, laboratory rat, transfection, voltage /patch clamp, western blotting
Project start date: 2003-02-01
Project end date: 2008-01-31
1R01NS045644-01 (2003): $252700
Randy A Hall
Emory University
Project start date: 2011-06-01
Project end date: 2016-02-29
Direct Interaction Between GABA-A And GABA-B Receptors
Randy A Hall, Associate Professor
Emory University 1599 Clifton Road, 4th Floor Atlanta, Ga 30322
Grant 5R01NS045644-05 from National Institute Of Neurological Disorders And Stroke IRG: MDCN
Keywords: receptor, G protein, GABA receptor, acid, analog, anxiety, barbiturate, benzodiazepine, biology, brain, cell, cell membrane, cell surface receptor, cell type, chloride channel, chronic pain, depression, epilepsy, health /scientific organization, immunoprecipitation, intracellular, ion, ligand, lighting, microscopy, neurotransmitter, pharmacology, phosphorylation, protein, receptor coupling, receptor expression, schizophrenia, tissue
Project start date: 2003-02-01
Project end date: 2008-01-31
5R01NS045644-05 (2007): $239605
Sponsored Links Excellgen http://Excellgen.com
5R01NS045644-04 (2006): $246761
5R01NS045644-03 (2005): $252700
5R01NS045644-02 (2004): $252700