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Molecular Studies Of T Cell Recognition And Cross-Reactivity: A Dissertation, Zu T. Shen Jul 2012

Molecular Studies Of T Cell Recognition And Cross-Reactivity: A Dissertation, Zu T. Shen

GSBS Dissertations and Theses

Intracellular pathogens are recognized by a specialized subset of lymphocytes known as CD8+ T cells. Pathogen recognition by CD8+ T cells occurs through binding of T cell receptors (TCR) to processed antigens in complex with major histocompatibility complex (MHC) class I proteins. TCR engagement of antigens in complex with MHC class I typically lead to cytotoxic CD8+ T cell responses, which result in pathogen clearance. Due to the large number of foreign antigens that might be encountered by any given host a diverse repertoire of TCRs must be available for immune recognition. The main source of TCR diversity is generated ...


Rna-Sensing Pattern Recognition Receptors And Their Effects On T-Cell Immune Responses: A Dissertation, Rachel F. Madera Jul 2012

Rna-Sensing Pattern Recognition Receptors And Their Effects On T-Cell Immune Responses: A Dissertation, Rachel F. Madera

GSBS Dissertations and Theses

Virus infection is sensed by the innate immune system through germline encoded pattern recognition receptors (PRRs). Toll-like receptors (TLRs), retinoic acid-inducible gene-I-like receptors (RLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs) serve as PRRs that recognize different viral components. Microbial nucleic acids such as Ribonucleic acid (RNA) are important virus-derived pathogen-associated molecular patterns (PAMPs) to be recognized by PRRs. Virus recognition may occur at multiple stages of the viral life cycle. Replication intermediates such as single-stranded RNA (ssRNA) and double-stranded RNA (dsRNA) are detected by the RNA-sensing PRRs that initiate innate and adaptive immune responses. Triggering of the innate immune system ...


Hiv-1 R5 Tropism: Determinants, Macrophages, And Dendritic Cells: A Dissertation, Thomas A. Musich May 2012

Hiv-1 R5 Tropism: Determinants, Macrophages, And Dendritic Cells: A Dissertation, Thomas A. Musich

GSBS Dissertations and Theses

Around thirty years ago HIV-1 was identified, and from that point the known epidemic has grown to over 30 million infected individuals. Early on in the course of HIV-1 research, viruses were classified as either syncytia inducing, CXCR4-using, T-cell tropic or non-syncytia inducing, CCR5-using, macrophage tropic. Since that time, several groups have shown that this is an oversimplification. There is a great deal of diversity amongst CCR5-using HIV-1 variants. There remains a great deal to be discovered regarding HIV-1 CCR5-tropism and how this affects other aspects of HIV-1 infection.

The CD4 binding site (CD4bs) on the HIV-1 envelope plays a ...


Molecular Mechanisms Of Endocytosis: Trafficking And Functional Requirements For The Transferrin Receptor, Small Interfering Rnas And Dopamine Transporter: A Dissertation, Deanna M. Navaroli Apr 2012

Molecular Mechanisms Of Endocytosis: Trafficking And Functional Requirements For The Transferrin Receptor, Small Interfering Rnas And Dopamine Transporter: A Dissertation, Deanna M. Navaroli

GSBS Dissertations and Theses

Endocytosis is an essential function of eukaryotic cells, providing crucial nutrients and playing key roles in interactions of the plasma membrane with the environment. The classical view of the endocytic pathway, where vesicles from the plasma membrane fuse with a homogenous population of early endosomes from which cargo is sorted, has recently been challenged by the finding of multiple subpopulations of endosomes. These subpopulations vary in their content of phosphatidylinositol 3- phosphate (PI3P) and Rab binding proteins. The role of these endosomal subpopulations is unclear, as is the role of multiple PI3P effectors, which are ubiquitously expressed and highly conserved ...


Localization Of Insulin Receptor Substrate-2 In Breast Cancer: A Dissertation, Jennifer L. Clark Mar 2012

Localization Of Insulin Receptor Substrate-2 In Breast Cancer: A Dissertation, Jennifer L. Clark

GSBS Dissertations and Theses

The insulin-like growth factor-1 receptor (IGF-1R) and many of its downstream signaling components have long been implicated in tumor progression and resistance to therapy. The insulin receptor substrate-1 (IRS-1) and IRS-2 adaptor proteins are two of the major downstream signaling intermediates of the IGF-1R. Despite their considerable homology, previous work in our lab and others has shown that IRS-1 and IRS-2 play divergent roles in breast cancer cells. Signaling through IRS-1 promotes cell proliferation, whereas signaling through IRS-2 promotes cell motility and invasion, as well as glycolysis. Moreover, using a mouse model of mammary tumorigenesis, our lab demonstrated that IRS-2 ...


Herbal Marijuana Alternatives Investigation: K2 And Spice: A Masters Thesis, Christopher D. Rosenbaum Dec 2011

Herbal Marijuana Alternatives Investigation: K2 And Spice: A Masters Thesis, Christopher D. Rosenbaum

GSBS Dissertations and Theses

Background

Herbal marijuana alternatives (HMA), legal plant products adulterated with synthetic cannabinoid receptor agonists, represent a growing public health concern. Only a few case reports describe HMA and synthetic cannabinoid’s clinical toxicity. We describe an outbreak of HMA abuse primarily in the Midwest, the clinical presentation of HMA toxicity, and clinical and forensic testing.

Methods

During the course of ongoing surveillance for emerging drugs of abuse between November 2009 and August 2010, we retrospectively and prospectively identified a convenience sample comprising 81 cases of abuse of HMA products. Subject demographics, vital signs, lab results and urine were obtained (when ...


Nuclear Import Of Smad: A Dissertation, Xiaochu Chen Aug 2011

Nuclear Import Of Smad: A Dissertation, Xiaochu Chen

GSBS Dissertations and Theses

Signal transduction by transforming growth factor β (TGF-β) cytokines is mediated by an evolutionarily conserved mechanism that depends on the Smad proteins to transduce an extracellular stimulus into the nucleus. In the unstimulated state, Smads spontaneously shuttle across the nuclear envelope and distribute throughout the cell. Upon TGF-β or bone morphogenetic protein (BMP) stimulation, the receptor-activated Smads are phosphorylated, assemble into complexes with Smad4, and become mostly localized in the nucleus. Such signal-induced nuclear translocation of activated Smads is essential for TGF-β–dependent gene regulation that is critical for embryonic development and homeostasis. The molecular machinery responsible for this process ...


Digital And Analog Stat5 Signaling In Erythropoiesis: A Dissertation, Ermelinda Porpiglia Aug 2011

Digital And Analog Stat5 Signaling In Erythropoiesis: A Dissertation, Ermelinda Porpiglia

GSBS Dissertations and Theses

Erythropoietin (Epo) modulates red blood cell production (erythropoiesis) by binding to its receptor and activating STAT5, a Signal Transducer and Activator of Transcription (STAT) protein implicated in both basal and stress erythropoiesis. Epo concentration in serum changes over three orders of magnitude, as it regulates basal erythropoiesis and its acceleration during hypoxic stress. However, it is not known how STAT5 translates the changes in Epo concentration into the required erythropoietic rates. We addressed this question by studying STAT5 phosphorylation, at the single cell level, in developing erythroblasts.

We divided erythroid progenitors in tissue into several flow-cytometric subsets and found that ...


Regulation And Function Of Neuronal Nicotinic Acetylcholine Receptors In Lung Cancer: A Dissertation, Ma. Reina D. Improgo Aug 2011

Regulation And Function Of Neuronal Nicotinic Acetylcholine Receptors In Lung Cancer: A Dissertation, Ma. Reina D. Improgo

GSBS Dissertations and Theses

Lung cancer is the leading cause of cancer-related mortality worldwide. The main risk factor associated with lung cancer is cigarette smoking. Research through the years suggests that nicotine in cigarettes promotes lung cancer by activating signaling pathways that lead to cell proliferation, cell survival, angiogenesis, and metastasis. Nicotine’s cellular actions are mediated by its cognate receptors, nicotinic acetylcholine receptors (nAChRs). Here, I describe the expression levels of all known human nAChR subunit genes in both normal and lung cancer cells. Of note, the genes encoding the α5, α3, and β4 subunits (CHRNA5/A3/B4) are over-expressed in small cell ...


Tyraminergic G Protein-Coupled Receptors Modulate Locomotion And Navigational Behavior In C. Elegans: A Dissertation, Jamie L. Donnelly Aug 2011

Tyraminergic G Protein-Coupled Receptors Modulate Locomotion And Navigational Behavior In C. Elegans: A Dissertation, Jamie L. Donnelly

GSBS Dissertations and Theses

An animal’s ability to navigate through its natural environment is critical to its survival. Navigation can be slow and methodical such as an annual migration, or purely reactive such as an escape response. How sensory input is translated into a fast behavioral output to execute goal oriented locomotion remains elusive. In this dissertation, I aimed to investigate escape response behavior in the nematode C. elegans. It has been shown that the biogenic amine tyramine is essential for the escape response. A tyramine-gated chloride channel, LGC-55, has been revealed to modulate suppression of head oscillations and reversal behavior in response ...


Nucleic Acid Sensing By The Immune System: Roles For The Receptor For Advanced Glycation End Products (Rage) And Intracellular Receptor Proteins: A Dissertation, Cherilyn M. Sirois Jul 2011

Nucleic Acid Sensing By The Immune System: Roles For The Receptor For Advanced Glycation End Products (Rage) And Intracellular Receptor Proteins: A Dissertation, Cherilyn M. Sirois

GSBS Dissertations and Theses

As humans, we inhabit an environment shared with many microorganisms, some of which are harmless or beneficial, and others which represent a threat to our health. A complex network of organs, cells and their protein products form our bodies’ immune system, tasked with detecting these potentially harmful agents and eliminating them. This same system also serves to detect changes in the healthy balance of normal functions in the body, and for repairing tissue damage caused by injury. Immune recognition of nucleic acids, DNA and RNA, is one way that the body detects invading pathogens and initiates tissue repair. A number ...


Dynamics Of Erythropoietic Survival Pathways In Vivo: A Dissertation, Miroslav Koulnis Jul 2011

Dynamics Of Erythropoietic Survival Pathways In Vivo: A Dissertation, Miroslav Koulnis

GSBS Dissertations and Theses

Erythropoiesis maintains stable tissue oxygenation in the basal state, while accelerating red cell production in anemia, blood loss or high altitude. The principal regulator of erythropoiesis is the hormone erythropoietin (Epo). In response to hypoxic stress, Epo can increase a 1000-fold, driving erythropoietic rate by up to 10-fold. It’s been suggested that survival pathways activated by the Epo receptor (EpoR) underlie its regulation of erythropoietic rate. A number of apparently redundant EpoR survival pathways were identified in vitro, raising the possibility of their functional specialization in vivo.

Here I assessed the roles of three survival pathways activated by EpoR ...


Blocking The Notch Pathway With Gamma-Secretase Inhibitors Enhances Temozolomide Treatment Of Gliomas Through Therapy-Induced Senescence: A Dissertation, Candace A. Gilbert May 2011

Blocking The Notch Pathway With Gamma-Secretase Inhibitors Enhances Temozolomide Treatment Of Gliomas Through Therapy-Induced Senescence: A Dissertation, Candace A. Gilbert

GSBS Dissertations and Theses

Glioma therapy relies on induction of cytotoxicity; however, the current combination of surgery, irradiation (IR) and temozolomide (TMZ) treatment does not result in a long-term cure. Our lab previously demonstrated that a small population of glioma cells enters a transient cell cycle arrest in response to chemotherapy. Treatment with TMZ significantly decreases initial neurosphere formation; however, after a short recovery period, a small number of cells resume neurosphere formation and repopulate the culture. This recovery of neurosphere growth recapitulates the inevitable glioma recurrence in the clinic. The focus of our laboratory is to study direct-target therapies that can be combined ...


A Tale Of Two Snps: Polymorphism Analysis Of Toll-Like Receptor (Tlr) Adapter Proteins: A Dissertation, Kamalpreet Nagpal May 2011

A Tale Of Two Snps: Polymorphism Analysis Of Toll-Like Receptor (Tlr) Adapter Proteins: A Dissertation, Kamalpreet Nagpal

GSBS Dissertations and Theses

The innate immune system is the first line of defense against invading pathogens. Recognition of microbial ligands by the innate immune system relies on germ-line encoded, evolutionarily conserved receptors called pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are one such family of PRRs and are involved in innate defenses to a variety of microbes. At the core of TLR signaling pathways are Toll interleukin-1 receptor (TIR) domain containing adapter proteins. Much of the specificity of TLR pathways arise from the differential use of these adapter proteins.

The TLR signaling cascade that ensues upon ligand recognition is marked by finely orchestrated ...


Hsp90-Mediated Maturation Of Kinases And Nuclear Steroid Hormone Receptors: A Dissertation, Natalie W. Pursell Apr 2011

Hsp90-Mediated Maturation Of Kinases And Nuclear Steroid Hormone Receptors: A Dissertation, Natalie W. Pursell

GSBS Dissertations and Theses

Among heat shock proteins, Hsp90 is unusual because it is not required for the proper folding of most cellular proteins but rather is disproportionally linked to the activation of signal transduction proteins including over forty kinases and many steroid hormone receptors. Mutated forms of many Hsp90 clients are causative agents in cancer, making Hsp90 a promising pharmacological target. Many small molecular inhibitors have been identified that competitively bind to the ATP binding site of Hsp90, some of which are in clinical trials as anticancer agents. Although the activation of kinase and hormone receptor clients by Hsp90 and its co-chaperones has ...


Cooperating Events In Core Binding Factor Leukemia Development: A Dissertation, Dmitri Madera Mar 2011

Cooperating Events In Core Binding Factor Leukemia Development: A Dissertation, Dmitri Madera

GSBS Dissertations and Theses

Leukemia is a hematopoietic cancer that is characterized by the abnormal differentiation and proliferation of hematopoietic cells. It is ranked 7th by death rate among cancer types in USA, even though it is not one of the top 10 cancers by incidence (USCS, 2010). This indicates an urgent need for more effective treatment strategies. In order to design the new ways of prevention and treatment of leukemia, it is important to understand the molecular mechanisms involved in development of the disease.

In this study, we investigated mechanisms involved in the development of acute myeloid leukemia (AML) that is associated ...


Neuronal Nicotinic Acetylcholine Receptors: Molecular Targets For Alcoholism And Ethanol Reward: A Dissertation, Linzy M. Hendrickson Jan 2011

Neuronal Nicotinic Acetylcholine Receptors: Molecular Targets For Alcoholism And Ethanol Reward: A Dissertation, Linzy M. Hendrickson

GSBS Dissertations and Theses

While it is clear that most drugs of abuse act to increase extracellular dopamine levels in the nucleus accumbens (NAc), the molecular mechanisms mediating this process vary depending on the molecular target each drug acts on. The rewarding properties of most drugs of abuse including cocaine, amphetamine, and heroin have been well established for some time; however, the molecular mechanisms by which ethanol acts to mediate reward have not been fully elucidated. In this thesis, I have examined the role of nicotinic acetylcholine receptors (nAChRs), known molecular targets for nicotine addiction, in mediating the initial rewarding properties of alcohol. Using ...


Elucidating The Transcriptional Network Underlying Expression Of A Neuronal Nicotinic Receptor Gene: A Dissertation, Michael D. Scofield Sep 2010

Elucidating The Transcriptional Network Underlying Expression Of A Neuronal Nicotinic Receptor Gene: A Dissertation, Michael D. Scofield

GSBS Dissertations and Theses

Neuronal nicotinic acetylcholine receptors (nAChRs) are involved in a plethora of fundamental biological processes ranging from muscle contraction to the formation of memories. The studies described in this work focus on the transcriptional regulation of the CHRNB4 gene, which encodes the ß4 subunit of neuronal nAChRs. We previously identified a regulatory sequence (5´– CCACCCCT –3´), or “CA box”, critical for CHRNB4 promoter activity in vitro. Here I report transcription factor interaction at the CA box along with an in vivo analysis of CA box transcriptional activity. My data indicate that Sp1, Sp3, Sox10 and c-Jun interact with the CHRNB4 CA ...


Dissecting The Role Of Innate Pattern Recognition Receptors And Interferon Regulatory Factor-5 In The Immune Response To Human Metapneumovirus And Other Pathogens: A Dissertation, Zhaozhao Jiang Aug 2010

Dissecting The Role Of Innate Pattern Recognition Receptors And Interferon Regulatory Factor-5 In The Immune Response To Human Metapneumovirus And Other Pathogens: A Dissertation, Zhaozhao Jiang

GSBS Dissertations and Theses

The Innate immune system is the first line of defense against invading microbial pathogens. It is a fast-acting and non-antigen-specific defense system, which employs germline encoded surveillance systems capable of responding to a broad-spectrum of pathogens. The innate immune system involves a variety of immune cells, which express different profiles of surveillance or detection receptors. Upon sensing pathogens, these receptors trigger cell signalling to turn on transcription of inflammatory cytokines, chemokines, anti-microbial peptides and type I Interferons. These effectors have direct effects on the control of pathogen load and also activate the adaptive immune system, which is ultimately required to ...


C. Elegans Metabolic Gene Regulatory Networks: A Dissertation, H. Efsun Arda Jul 2010

C. Elegans Metabolic Gene Regulatory Networks: A Dissertation, H. Efsun Arda

GSBS Dissertations and Theses

In multicellular organisms, determining when and where genes will be expressed is critical for their development and physiology. Transcription factors (TFs) are major specifiers of differential gene expression. By establishing physical contacts with the regulatory elements of their target genes, TFs often determine whether the target genes will be expressed or not. These physical and/or regulatory TF-DNA interactions can be modeled into gene regulatory networks (GRNs), which provide a systems-level view of differential gene expression. Thus far, much of the GRN delineation efforts focused on metazoan development, whereas the organization of GRNs that pertain to systems physiology remains mostly ...


A View Of The Imd Pathway From The Rhim, Kamna Aggarwal Mar 2010

A View Of The Imd Pathway From The Rhim, Kamna Aggarwal

GSBS Dissertations and Theses

Innate immunity is the first line of defense against invading pathogens. It functions to eliminate pathogens and also to control infections. The innate immune response is also important for the development of pathogen-specific adaptive immune responses. As a result, the study of innate immune signaling pathways is crucial for understanding the interactions between host and pathogen. Unlike mammals, insects lack a classical adaptive immune response and rely mostly on innate immune responses.

Innate immune mechanisms have been widely studied in the fruit fly, Drosophila melanogaster. The genetic and molecular tools available in the Drosophila system make it an excellent model ...


Maintenance Of Visual Sensitivity In The Drosophila Eye: A Dissertation, Lina Ni Jan 2010

Maintenance Of Visual Sensitivity In The Drosophila Eye: A Dissertation, Lina Ni

GSBS Dissertations and Theses

High visual sensitivity is a common but important characteristic of animal eyes. It is especially critical for night vision. In animal eyes, photoreceptors are the first to receive the incoming rays of light and they convert the light signals to electrical signals before passing the information to interneurons in the eye and finally to the brain.

To function in dim light conditions, photoreceptors have developed high sensitivities to light. It is reported that both mammalian rod photoreceptors and Drosophilaphotoreceptors can detect single photons.

The high sensitivities of photoreceptors largely depend on a high content of rhodopsin, a light-stimulated G ...


Characterization Of The Nef-Tcr Zeta Interaction And Its Role In Modulation Of Src Family Kinase Activity: A Dissertation, Walter Minsub Kim Aug 2009

Characterization Of The Nef-Tcr Zeta Interaction And Its Role In Modulation Of Src Family Kinase Activity: A Dissertation, Walter Minsub Kim

GSBS Dissertations and Theses

One of the hallmarks of an infection with pathogenic HIV-1 is the elevated level of immune activation that leads to rapid progression to AIDS. Surprisingly, nonhuman primates naturally infected with SIV do not exhibit an augmented activation phenotype nor severe immunodeficiency. One of the viral components implicated in determining the state of immune activation is the accessory protein Nef which has been demonstrated to affect T cell signaling pathways from within the intracellular compartment and for Nef from SIV, to downregulate TCR surface expression. Recently, Nef from HIV-1 and SIV have been demonstrated to bind the ζ chain of the ...


Functional Elements Of EspfU, An Enterohemorrhagic E. Coli Effector That Stimulates Actin Assembly: A Dissertation, Brian M. Skehan Jun 2009

Functional Elements Of EspfU, An Enterohemorrhagic E. Coli Effector That Stimulates Actin Assembly: A Dissertation, Brian M. Skehan

GSBS Dissertations and Theses

Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is an attaching and effacing pathogen that upon attachment to host cells, induce characteristic attaching and effacing lesions and formation of F-actin rich pedestals beneath sites of bacterial attachment. EHEC harbors a Type III secretion system through which it delivers dozens of effectors into the host cell. The two secreted effectors critical for EHEC-mediated actin pedestal formation are the translocated intimin receptor (Tir) and EspFU. EspFU consists of an N-terminal secretion signal and a C-terminus containing six tandem 47-residue proline-rich repeats, each of which can bind and activate the actin nucleation promoting ...


Functional Analysis Of Yeast Pheromone Receptors In Er Exit, Ligand-Induced Endocytosis And Oligomerization: A Dissertation, Chien-I Chang May 2009

Functional Analysis Of Yeast Pheromone Receptors In Er Exit, Ligand-Induced Endocytosis And Oligomerization: A Dissertation, Chien-I Chang

GSBS Dissertations and Theses

This study investigates endocytosis and ER export signals of the yeast α-factor receptor and the role that receptor oligomerization plays in these processes. The α-factor receptor contains signal sequences in the cytoplasmic C-terminal domain that are essential for ligand-mediated endocytosis. In an endocytosis complementation assay, I found that oligomeric complexes of the receptor undergo ligand-mediated endocytosis when the α-factor binding site and the endocytosis signal sequences are located in different receptors. Both in vitro and in vivo assays strongly suggested that ligand-induced conformational changes in one Ste2 subunit do not affect neighboring subunits. Therefore, the recognition of endocytosis signal sequence ...


Chromatin Remodeling In Transgenic Mouse Brain: Implications For The Neurobiology Of Depression: A Dissertation, Yan Jiang May 2009

Chromatin Remodeling In Transgenic Mouse Brain: Implications For The Neurobiology Of Depression: A Dissertation, Yan Jiang

GSBS Dissertations and Theses

Histone lysine methylation is an important epigenetic mark for regulation of gene expression and chromatin organization. Setdb1 (Set domain, bifurcate 1), one of the histone lysine methyltransferases, specifically methylates histone H3 at lysine 9 (H3K9) and participates in transcriptional repression and heterochromatin formation. The major task of my thesis work was to investigate the epigenetic roles of Setdb1 in regulating brain functions. I started my thesis work by examining Setdb1 expression pattern during mouse brain development. The most robust signal of Setdb1 was detected in the fetal brains at embryonic day 12.5, with a ubiquitous distribution in all the ...


Role Of Endoplasmic Reticulum Stress Response Signaling In T Cells: A Dissertation, Steven C. Pino Jul 2008

Role Of Endoplasmic Reticulum Stress Response Signaling In T Cells: A Dissertation, Steven C. Pino

GSBS Dissertations and Theses

T cells play a central role in cellular-mediated immunity and must become activated to participate as effector cells in the immune response. The activation process is highly intricate and involves stimulation of a number of downstream signaling pathways enabling T cells to proliferate and produce cytokines that are vital for proper effector function. This increase in protein production and protein folding activity adds to the normal physiological strain on cellular machinery. One cellular compartment that has generated a mechanism to mitigate the stress induced by increased protein production is the endoplasmic reticulum (ER).

In general, an increase in cellular production ...


The Role Of Tec Family Kinases In Innate T Cell Development And Function: A Dissertation, Martin Felices Jun 2008

The Role Of Tec Family Kinases In Innate T Cell Development And Function: A Dissertation, Martin Felices

GSBS Dissertations and Theses

The Tec family kinases Itk and Rlk have been previously shown to have an important role in signaling downstream of the T cell receptor [TCR]. Almost all of the work done in the past on these two kinases looked at their role in conventional αβ T cells, specifically CD4+ T cells. These studies demonstrated functions for Itk [primarily] and Rlk in T cell development, activation, and differentiation. However, despite the wealth of knowledge on conventional CD4+ T cells, prior to the work presented here little to no studies addressed the role of Tec family kinases on CD8+ or innate T ...


Analysis Of Cpeb Family Protein Member Cpeb4 Function In Mammalian Neurons: A Dissertation, Ming-Chung Kan Jun 2008

Analysis Of Cpeb Family Protein Member Cpeb4 Function In Mammalian Neurons: A Dissertation, Ming-Chung Kan

GSBS Dissertations and Theses

Local protein synthesis is required for long-term memory formation in the brain. One protein family, Cytoplasmic Polyadenylation Element binding Protein (CPEB) that regulates protein synthesis is found to be important for long-term memory formation possibly through regulating local protein synthesis in neurons. The well-studied member of this family, CPEB1, mediates both translational repression and activation of its target mRNAs by regulating mRNA polyadenylation. Mouse with CPEB1 KO shows defect in memory extinction but not long-term memory formation. Three more CPEB1 homologs (CPEB2-4) are identified in mammalian system. To test if CPEB2-4 may have redundant role in replacing CPEB1 in mediating ...


Modulation Of Neuropeptide Release Via Voltage-Dependent And -Independent Signaling In Isolated Neurohypophysial Terminals: A Dissertation, Cristina M. Velazquez-Marrero Apr 2008

Modulation Of Neuropeptide Release Via Voltage-Dependent And -Independent Signaling In Isolated Neurohypophysial Terminals: A Dissertation, Cristina M. Velazquez-Marrero

GSBS Dissertations and Theses

This thesis details my examination of several mechanisms for modulation of neuropeptide release via voltage-dependent and voltage-independent intraterminal signaling in isolated neurohypophysial terminals. The first part of this work characterizes depolarization-induced neuropeptide release in the absence of extracellular calcium. The goal of this project was to examine the relationship between depolarization-induced release of intracellular calcium stores and depolarization-secretion coupling of neuropeptides. We demonstrate that depolarization in the absence of extracellular calcium induced by either High K+ or electrical stimulation induces a rise in [Ca2+]i and subsequent neuropeptide release from Hypothalamic Neurohypophysial System (HNS) terminals. A portion of extracellular ...