Browsing Pharmacology by Title
Now showing items 4-23 of 82
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Broadband Tuning the Voltage Dependence of a Sodium Channel
Mammalian voltage-gated sodium channels are comprised of four homologous domains, each containing a functionally distinct voltage-sensing domain (VSD). In contrast, the bacterial sodium channel NaVAb is a homotetramer, ... -
Characterization of a novel deafwaddler mutant implicates a role for PMCA2 regulation in the interaction with cadherin 23 and resulting auditory phenotype
(2013-07-25)The transport of calcium ions across a cell membrane is critical for cell signaling in eukaryotic organisms. Maintenance of a low intracellular concentration is necessary for recognition of the calcium signal and, conversely, ... -
Characterization of molecular forms of G protein-coupled receptor kinase 1 (rhodopsin kinase) in vertebrate retina and pineal gland
(1997)The purpose of my dissertation was to investigate the presence of molecular forms of G protein-coupled receptor kinase 1 (GRK1), and their functions in photoreceptor cells of the vertebrate retina and the pineal gland.GRK1 ... -
A characterization of the expression, regulation, and function of the mouse voltage-sensitive phosphatase, Mm-VSP
Voltage-sensitive phosphatases (VSPs) are proteins that directly couple changes in membrane electrical potential to changes in the enzymatic activity of a lipid phosphatase domain. The best characterized activity of VSPs ... -
Characterization of Ubiquitin-mediated Protein Quality Control in the Nucleus
(2012-09-13)Due to the importance of proper protein folding, cells have evolved a collection of protein quality control (PQC) mechanisms that maintain overall cellular protein homeostasis. One type of PQC is ubiquitin-proteasome ... -
Characterizing the role of protein deubiquitination in ribosome biogenesis
(2012-08-10)Eukaryotic ribosome biogenesis requires hundreds of trans-acting factors and dozens of RNAs. Although most factors required for ribosome biogenesis have been identified, little is known about how they are regulated. Here, ... -
Characterizing the role of sodium channels in mouse models of Dravet Syndrome
(2013-02-25)Voltage-gated sodium channels (Nav) are responsible for the initiation and propagation of action potentials in excitable cells. The channels isoforms Nav1.1, Nav1.2, Nav1.3 and Nav1.6 are dynamically expressed in the ... -
Combinatorial strategies using CRISPR/Cas9 for gene mutagenesis in adult mice
A major challenge to understanding how genes modulate complex behaviors is the inability to restrict genetic manipulations to defined cell populations or circuits. To circumvent this, we created a simple strategy for ... -
CRL3 and CRL4 are functionally diverse ubiquitination complexes that regulate fundamental cell processes from human DNA damage repair to plant pathogen immunity
Ubiquitination is a mechanism used by eukaryotes to precisely alter the level, functionality, and location of specific target proteins through the post-translational attachment of one or more ubiquitin tags. This attachment ... -
Decoding protein kinase signaling during mitosis: Exploiting molecular scaffolds and developing drug-targeting tools for studying local kinase biology
Fundamental cellular processes such as cell division, migration, differentiation, and growth require environmental signals to be converted into chemical responses that generate biological outputs. Accordingly, these events ... -
Depletion of dAKAP1 signaling complexes accompanies pathological changes in mitochondrial dynamics during breast cancer progression
The dual-specificity A-kinase anchoring protein 1 (dAKAP1) is a mitochondrial anchoring protein responsible for recruiting protein kinase A (PKA), along with other signaling molecules, to the outer mitochondrial membrane ... -
Development of analytical tools to enrich and identify protein dopaminylation
Dopamine homeostasis and oxidative stress are thought to be key players in the etiology of Parkinson’s disease (PD). PD is a disorder characterized by the death of dopaminergic neurons in the substantia nigra and the ... -
Development of Oligonucleotide-directed proximity-interactome MAPping (O-MAP), for characterizing RNA-protein interactions and higher order subnuclear architecture in situ
RNA-protein interactions underscore a broad array of regulatory mechanisms throughout biology, and dysregulation of these interactions contributes to a broad range of human pathologies such as neurodegenerative disorders ... -
Developmental expression and functions of voltage-gated potassium channels in normal and mutant mice
(1999)Kv1.1, a Shaker-like voltage-gated potassium channel, is strongly expressed in a variety of neurons in adult rodents, where it appears to be involved in regulating neuronal excitability. Here we show that Kv1.1 is also ... -
Diametric Changes in Ventral Striatal Dopamine Release Regulate Drug-Taking and Drug-Seeking Behavior
The overall goal of this dissertation work was to determine how drug-cue elicited phasic dopamine neurotransmission changes over prolonged drug use, in both drug-taking and drug-seeking contexts. My initial work, done in ... -
A Differential Requirement for Cdc48/p97 and Protein Chaperones in Nuclear Protein Quality Control Degradation
(2013-07-25)The ubiquitin-proteasome system is one of the principal means for the destruction of misfolded proteins in the cell. In addition to the core enzymes within the ubiquitination cascade and the 26S proteasome, many ancillary ... -
Discovery of novel TAF1 DNA binding domains in TFIID promoter recognition and gene transcription
The central dogma of biology describes the basic flow of genetic information starting from DNA, which is converted to message RNA, then into functional proteins. This classical view provides a framework for how a cell can ... -
Divergent medial amygdala circuits for resolving approach-avoidance conflict
Avoidance of innate threats is often conflicted by motivations to engage in exploratory approach behavior. The neural circuits that underlie this approach-avoidance conflict are not well resolved. Here, we isolated a ... -
Effects of GLT-1 loss on central nervous system insulin signaling and implications for Alzheimer’s disease pathogenesis
Regulation of glutamatergic neurotransmission in the central nervous system (CNS) by glutamate transporters allows for the fine balance between tightly regulated signaling and prevention of glutamate-induced neurotoxicity. ... -
Elucidating Levetiracetam action at the presynaptic terminal
Levetiracetam (KeppraTM, LEV) is the first of a growing class of anti-epileptic drugs that shows great promise in the treatment of multiple neurological disorders. LEV has a unique receptor, Synaptic Vesicle Protein 2A ...