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Articles 31 - 57 of 57

Full-Text Articles in Cell and Developmental Biology

Characterization Of The Whale Shark (Rhincodon Typus) Melanocortin-2 Receptor, Brianne Hoglin Jan 2021

Characterization Of The Whale Shark (Rhincodon Typus) Melanocortin-2 Receptor, Brianne Hoglin

Electronic Theses and Dissertations

Among bony vertebrates, the melanocortin-2 receptor ortholog is unique among the family of five melanocortin receptors on the basis that it is dependent on its accessory protein, MRAP1, for trafficking and activation, and is selective for activation by ACTH alone. Previous studies on the MC2R orthologs of select cartilaginous fish, the elephant shark (Callorhinchus milii) and the red stingray (Dasyatis akajei), revealed divergent traits in a less obligatory relationship on MRAP1 and its ability to be activated by ACTH or the MSH-sized peptides. However, observed traits were not consistent between these two cartilaginous fish species, posing …


Rab35 Centered Membrane Trafficking Pathway Directs Apical Constriction During Drosophila Gastrulation, Hui Miao Jan 2021

Rab35 Centered Membrane Trafficking Pathway Directs Apical Constriction During Drosophila Gastrulation, Hui Miao

Electronic Theses and Dissertations

Force generation in epithelial tissues is often pulsatile, with actomyosin networks generating high-tension contractile forces at the cell cortex before cyclically disassembling. This pulsed nature of cytoskeletal forces implies that there must be cellular processes to extract unidirectional changes that drive processive transformations in cell shape. During Drosophila melanogastergastrulation, the invagination of the prospective mesoderm is driven by the pulsed constriction of apical surfaces. Here, we address the mechanisms by which the irreversibility of pulsed events is achieved while also permitting uniform epithelial behaviors to emerge. We use MSD-based analyses to identify contractile steps and find that when a …


Fxs-Causing Point Mutations In Fmrp Disrupt Neuronal Granule Formation And Function, Emily L. Starke Jan 2021

Fxs-Causing Point Mutations In Fmrp Disrupt Neuronal Granule Formation And Function, Emily L. Starke

Electronic Theses and Dissertations

Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by the disruption of Fragile X Mental Retardation Protein (FMRP) function in neurons, affecting nearly 1 in 7,500 individuals. Although FXS typically occurs from a complete loss of FMRP expression due to a CGG trinucleotide expansion within the 5’UTR of the FMR1 gene, single nucleotide polymorphisms (SNPs) within the KH domains of FMRP have been shown to severely disrupt FMRP function. FMRP is an RNA-binding translation repressor that interacts with ~4% of the neuronal transcriptome. Many target mRNAs encode for proteins important for regulating synaptic processes and modulate synaptic plasticity. It …


Analyzing The Effect On Ligand Sensitivity For Xenopus Tropicalis Mc1r, Mc3r, Mc4r, And Mc5r As A Result Of Coexpression With Gallus Gallus Mrap1 In Chinese Hamster Ovary Cells, Avery Niemann, Robert Dores Jan 2020

Analyzing The Effect On Ligand Sensitivity For Xenopus Tropicalis Mc1r, Mc3r, Mc4r, And Mc5r As A Result Of Coexpression With Gallus Gallus Mrap1 In Chinese Hamster Ovary Cells, Avery Niemann, Robert Dores

DU Undergraduate Research Journal Archive

Some melanocortin receptors and the accessory protein MRAP1 have been found to interact in novel ways when co-expressed in the same cells following stimulation with either ACTH (1-24) or αMSH. These interactions have been seen for mammalian, bird, and some bony fish melanocortin receptors. Such analysis has not been done yet on the amphibian melanocortin receptors, MC1R, MC3R, MC4R, and MC5R. To this end, this study was done on the effects regarding ligand sensitivity for ACTH (1-24) and αMSH, when the MC1R, MC3R, MC4R, and MC5R paralogs of the amphibian, Xenopus tropicalis were expressed in Chinese Hamster Ovary cells either …


Quantification Of Mitochondrial Zinc Homeostasis And Analysis Of Zinc And Polyamine-Mediated Axonal Trafficking, Dylan Hunt Fudge Jan 2020

Quantification Of Mitochondrial Zinc Homeostasis And Analysis Of Zinc And Polyamine-Mediated Axonal Trafficking, Dylan Hunt Fudge

Electronic Theses and Dissertations

The zinc ion is an important emerging signaling molecule for biological processes. In this work we engineered improved zinc sensors based on our previously developed fluorescent sensor GZnP1 to provide sensors with a higher fluorescent readout, faster kinetics, and a superior sensitivity to zinc. We utilized these zinc sensors and further developed the sensors to answer questions pertaining to biological zinc. We showed the labile zinc concentration in the mitochondrial matrix was less than 1 pM while the labile zinc concentration in the cytosol and mitochondrial IMS were comparable (~100 pM) across four different cell lines. Using these zinc sensors …


Cellular And Developmental Insights Into The Early Evolution Of Muscle, Jeffrey J. Colgren Jan 2020

Cellular And Developmental Insights Into The Early Evolution Of Muscle, Jeffrey J. Colgren

Electronic Theses and Dissertations

Whereas a great deal has been learned about the molecular underpinnings of morphological evolution in animals, much less is known about the origin of novel cell and tissue types. During the time in which the earliest animal lineages were diversifying, fundamental cell and tissue types, such as muscles, arose. Sponges are one of two animal lineages that lack muscles, yet they undergo coordinated full body contractions. Whereas the signaling processes have been studied, the physical mechanisms of contraction are completely uncharacterized. The main purpose of this work is to understand the primary contractile tissue of the sponge Ephydatia muelleri, …


Ehbp1 And Ehd2 Regulate Dll4 Caveolin-Mediated Endocytosis During Blood Vessel Development, Amelia Margaret Webb Jan 2020

Ehbp1 And Ehd2 Regulate Dll4 Caveolin-Mediated Endocytosis During Blood Vessel Development, Amelia Margaret Webb

Electronic Theses and Dissertations

During angiogenesis, the development of new blood vessels from existing vessels, there must be tight regulation between a leading tip cell and trailing stalk cells during vascular patterning. Lateral inhibition produced by Notch signaling is central to the specification and maintenance of tip and stalk cells in growing angiogenic sprouts. The Notch pathway is activated by the ligand Delta at adherens junctions between tip and stalk cells. Despite the centrality of Delta/Notch signaling to angiogenesis, relatively little is known about the mechanism of this signaling event. It has been proposed that the force generated by the Notch bound Delta ligand …


Sorting Of Cargo Proteins Within The Regulated Secretory Pathway: The Peripheral Membrane Protein Hid-1 As A Sorting And Vesicle Biogenesis Factor, Blake H. Hummer Jan 2020

Sorting Of Cargo Proteins Within The Regulated Secretory Pathway: The Peripheral Membrane Protein Hid-1 As A Sorting And Vesicle Biogenesis Factor, Blake H. Hummer

Electronic Theses and Dissertations

Large dense core vesicles (LDCVs) form at the trans-Golgi network (TGN) and mediate the regulated release of neuropeptides and peptide hormones. Despite their central role to physiology, the mechanisms controlling biogenesis and sorting to LDCVs is not well understood. Optimizing the retention using selective hooks (RUSH) method in neuroendocrine cells, we show it is possible to visualize sorting to the constitutive and regulated secretory pathways in real-time and that the bulk of transmembrane LDCV cargoes do not sort directly onto LDCVs, but exit the TGN into non-regulated vesicles to be incorporated to LDCVs at a later step. Additionally, we characterize …


Quantification Of Dynamic Epithelial Sheet Architecture In Botryllus Schlosseri Using 2-D & 3-D Image Analysis, Roopa Madhu Jan 2020

Quantification Of Dynamic Epithelial Sheet Architecture In Botryllus Schlosseri Using 2-D & 3-D Image Analysis, Roopa Madhu

Electronic Theses and Dissertations

Epithelial tubules form critical structures in various body tissues; how- ever, since they are difficult to access experimentally, their architecture and dynamics are not well understood. Here we examine the dynamic remodeling of epithelial tubes in vivo using a novel and uniquely accessible model system: the extracorporeal vasculature of Botryllus schlosseri (sea squirt). In Botryllus, massive retraction of blood vessels can be triggered without loss of barrier function, through (i) disrupting collagen crosslinking in the basement membrane using β-aminopropionitrile (BAPN); or (ii) disrupting the integrin pathway through inhibition of focal adhesion kinase (FAK). We performed stereographic projections of 3-dimensional …


Cellular And Organismal Ramifications Of De Novo Purine Synthesis Dysregulation, Randall Craig Mazzarino Jan 2020

Cellular And Organismal Ramifications Of De Novo Purine Synthesis Dysregulation, Randall Craig Mazzarino

Electronic Theses and Dissertations

Purines are a class of nitrogenous bases and are essential small molecules to life. Purines are used within the cell as genetic information carriers, energy currency, signaling molecules, and cofactors for multiple processes. They are formed through de novo and salvage pathways found in cells across the phylogenetic tree. The substrates of enzymes within de novo purine synthesis are known to influence other processes within the cell, such as energy homeostasis. In humans, de novo purine synthesis disorders are rare, with around 100 people identified. These patients exhibit a range of phenotypes, with varying degrees of mental retardation, seizure activity, …


Actin Regulation And Furrow Dynamics During Early Drosophila Embryogenesis, Yi Xie Jan 2020

Actin Regulation And Furrow Dynamics During Early Drosophila Embryogenesis, Yi Xie

Electronic Theses and Dissertations

Drosophila embryogenesis starts with a single nucleus undergo 13 rounds of nuclear divisions called syncytial cycles. Staring at cycle 10 when nuclei migrate to the surface of the embryo, massive and dynamic cortical actin structures and cleavage furrow formations occur. How actin regulators coordinate into an organized network directing three-dimension actin structures in the developing organisms is an unsolved question. Here, I present an in-depth characterization of actin cap dynamics: the actin caps go through expansion, stabilization, elongation and fragmentation phases in each cycle. Arp2/3 is the major contributor to actin cap formation. The functions of 7 different actin and …


New Insights Into Mycofactocin Biosynthesis, Structure And Function, Richard Selorm Ayikpoe Jan 2019

New Insights Into Mycofactocin Biosynthesis, Structure And Function, Richard Selorm Ayikpoe

Electronic Theses and Dissertations

Mycofactocin is a putative ribosomally synthesized and post-translationally modified peptide (RiPP)-derived redox cofactor. Its biosynthesis is accomplished through the dedicated actions of the products of six conserved genes, mftABCDEF. The mycofactocin pathway is one of the most widely distributed RiPP systems in bacteria however, this distribution is heavily skewed towards the Mycobacteria genus including human pathogenic variants such as M. tuberculosis and M. ulcerans. Gene expression studies have demonstrated the essentiality of the pathway in the ability of M. tuberculosis to utilize the host's cholesterol as sole carbon source during latency. However, the biosynthesis, structure and physiological function …


Transgenerational Effects Of Maternal Age On Offspring Fitness In Crickets, Jacob D. Wilson Jan 2019

Transgenerational Effects Of Maternal Age On Offspring Fitness In Crickets, Jacob D. Wilson

Electronic Theses and Dissertations

Advanced parental age is an important aspect of parental condition that can have both positive and negative effects on offspring fitness, and thus, parental age can be considered a parental effect. As a parental effect, parental age may affect a variety of offspring traits and may cascade to influence several generations of offspring. Given the complexities of studying both paternal and maternal age, we studied the effects of maternal age only. Using the Pacific field cricket, Teleogryllus oceanicus, we asked 1) does maternal age have influences over several generations of offspring and 2) does maternal age influence the reproductive …


Origins Of Animal Cell Adhesion, Jennyfer Mora Mitchell Jan 2018

Origins Of Animal Cell Adhesion, Jennyfer Mora Mitchell

Electronic Theses and Dissertations

A fundamental requirement for multicellularity is cell adhesion. This includes mechanisms by which cells adhere to each other and to their secreted extracellular matrix (ECM). Two well characterized adhesion complexes in animals include: 1) adherens junctions (AJs), which are involved in cell-cell adhesion and composed of cadherin receptors, p120-, α- and β-catenin, and 2) focal adhesions (FAs), which are involved in cell-ECM adhesion and include proteins such as integrins, vinculin, paxillin, talin and focal adhesion kinase (FAK). The molecular components of AJs are widely conserved in animals, and largely absent in non-animals. In contrast, the molecular components of FAs have …


Superresolved Three-Dimensional Analysis Of The Spatial Arrangement Of The Human Immunodeficiency Virus Type-1 (Hiv-1) Envelope Glycoprotein At Sites Of Viral Assembly, Carmen Anne Buttler Jan 2018

Superresolved Three-Dimensional Analysis Of The Spatial Arrangement Of The Human Immunodeficiency Virus Type-1 (Hiv-1) Envelope Glycoprotein At Sites Of Viral Assembly, Carmen Anne Buttler

Electronic Theses and Dissertations

Human Immunodeficiency Virus type 1 (HIV-1) replicates by forcing infected host cells to produce new virus particles, which assemble form protein components on the inner leaflet of the host cell's plasma membrane. This involves incorporation of the essential viral envelope glycoprotein (Env) into a structural lattice of viral Gag proteins. The mechanism of Env recruitment and incorporation is not well understood. To better define this process, we seek to describe the timing of Env-Gag encounters during particle assembly by measuring angular positions of Env proteins about the surfaces of budding particles. Using three-dimensional superresolution microscopy, we show that Env distributions …


Evaluating The Interaction Between The Human Melanocortin-2 Receptor And The Accessory Protein, Mrap1: Chimeric Receptor And Alanine Substitution Studies On Transmembrane Domain 4, Extracellular Loop 2, And Transmembrane Domain 5, Perry Victoria Davis Jan 2018

Evaluating The Interaction Between The Human Melanocortin-2 Receptor And The Accessory Protein, Mrap1: Chimeric Receptor And Alanine Substitution Studies On Transmembrane Domain 4, Extracellular Loop 2, And Transmembrane Domain 5, Perry Victoria Davis

Electronic Theses and Dissertations

The melanocortin-2 receptor (MC2R) is the most complex due to its trafficking and ligand selectivity requirements for proper activation. The MC2R requires the melanocortin receptor accessory protein-1 (MRAP1) for proper trafficking and activation of the receptor by the melanocortin hormone, ACTH. MRAP1 is a single transmembrane-spanning domain protein that creates a homodimer with another MRAP1 protein. Furthermore, MRAP2 creates a heterodimer with the MC2R. Previous studies have shown that the MRAP1 protein contains an activation motif required for activation of MC2R and this activation motif located on the extracellular space side of the plasma membrane of the cell. The objective …


Abnormal Dendritic Maturation Of Developing Cortical Neurons Exposed To Corticotropin Releasing Hormone (Crh): Insights Into Effects Of Prenatal Adversity?, Megan M. Curran, Curt A. Sandman, Elysia Poggi Davis, Laura M. Glynn, Tallie Z. Baram Jun 2017

Abnormal Dendritic Maturation Of Developing Cortical Neurons Exposed To Corticotropin Releasing Hormone (Crh): Insights Into Effects Of Prenatal Adversity?, Megan M. Curran, Curt A. Sandman, Elysia Poggi Davis, Laura M. Glynn, Tallie Z. Baram

Psychology: Faculty Scholarship

Corticotropin releasing hormone (CRH) produced by the hypothalamus initiates the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the body’s stress response. CRH levels typically are undetectable in human plasma, but during pregnancy the primate placenta synthesizes and releases large amounts of CRH into both maternal and fetal circulations. Notably, placental CRH synthesis increases in response to maternal stress signals. There is evidence that human fetal exposure to high concentrations of placental CRH is associated with behavioral consequences during infancy and into childhood, however the direct effects on of the peptide on the human brain are unknown. In this study, we used a …


Dense Core Vesicle Heterogeneity In Anterior Pituitary Cells, Kelly Sinak Jan 2017

Dense Core Vesicle Heterogeneity In Anterior Pituitary Cells, Kelly Sinak

Electronic Theses and Dissertations

Peptides, which are packaged in dense core vesicles, are an integral part of the function of the endocrine and neurological systems. The dense core vesicles function as an efficient form of peptide storage prior to regulated exocytosis. Two different dense core specific transmembrane proteins traffic different when comparted to retained prolactin cores, offering evidence of heterogeneity of vesicles within a single cell. By comparing synaptotagmin 1 and 7 distribution in male rat and lactating female lactotrophs, a distinct pattern emerges. Cells that retain prolactin cores after exocytosis correspond with those that contain synaptotagmin 1. This finding is a reversal for …


Akap150 Dynamics In Anterior Pituitary Cells, Kristen E. Dew Jan 2016

Akap150 Dynamics In Anterior Pituitary Cells, Kristen E. Dew

Electronic Theses and Dissertations

Cellular communication occurs as a result of changes in signaling pathways. A well-studied signaling pathway is through G protein coupled receptors (GPCRs). In gonadotropes, GPCR stimulation by GnRH leads to the activation of protein kinase A (PKA). Activated PKA can phosphorylate ion channels, potentially causing an influx of calcium, depolarization and secretion of hormones. A scaffolding protein known as AKAP150 anchors PKA near L-type calcium channels. In addition, AKAP150 anchors phosphatases, which provides temporal control during signaling events. It was recently shown that AKAP150 is mobile in neuronal dendrites, providing regulation to where the signaling cascade occurs in the cell. …


The Ecology And Evolution Of Rare, Soil Specialist Astragalus Plants In The Arid Western U.S., Joseph M. Statwick Jan 2016

The Ecology And Evolution Of Rare, Soil Specialist Astragalus Plants In The Arid Western U.S., Joseph M. Statwick

Electronic Theses and Dissertations

Organisms that specialize in uncommon habitats are, by their very nature, inherently uncommon. Specialization has its advantages, namely reduced competition and predation, but it also incurs costs. Specialists often have small population sizes, narrow ranges, and fragmented habitat, all of which engender negative consequences on an evolutionary timescale. Herein, I examine benefits and costs of specialization in selenium-hyperaccumulating plants in the genus Astragalus (Fabaceae). These plants are disproportionately likely to be rare and of conservation concern. Thus, I optimized germination pretreatments for Astragalus species such that seed loss can be minimized during ex situ cultivation, and found that physical scarification …


Regulation Of Synaptogenesis By The Mirna Pathway And Fmr/P Bodies, Jacqueline Rochelle Furlong Jan 2015

Regulation Of Synaptogenesis By The Mirna Pathway And Fmr/P Bodies, Jacqueline Rochelle Furlong

Electronic Theses and Dissertations

Post-transcriptional regulation of mRNA is facilitated by different mechanisms, such as microRNA (miRNA) induced gene silencing or fragile X mental retardation protein (FMRP) mediated repression either independent of or acting through cytoplasmic RNA Processing bodies (P bodies). DPTP99A, Lar, and Wg have known functions during synaptogenesis and may be targets of miR-8. Here, we provide evidence that miR-8 regulates DPTP99A in vitro. Non-endogenous miR-8 expressed using an UAS driver regulates Lar. Endogenous miR-8 may regulate DPTP99A in vivo. Here we show that FMRP is capable of colocalizing with the P body components: DCP1, HPat, and Me31B, but not …


Rab8 Directs Tubulation And Furrow Ingression During Epithelial Formation In Drosophila Melanogaster, Lauren Mackenzie Mavor Jan 2015

Rab8 Directs Tubulation And Furrow Ingression During Epithelial Formation In Drosophila Melanogaster, Lauren Mackenzie Mavor

Electronic Theses and Dissertations

One of the most fundamental changes in cell morphology is the formation of a plasma membrane furrow. The Drosophila embryo undergoes several cycles of rapid furrow ingression during early development, which culminates in the formation of an epithelial sheet. Previous studies have demonstrated the requirement for intracellular trafficking pathways in furrow ingression; however, the pathways that link compartmental behaviors with cortical furrow ingression events have remained unclear. This research shows that Rab8, a small GTPase associated with late exocytic trafficking events, demonstrates striking dynamic behaviors in vivo; transitioning from punctate structures to a stable association with the cortex during …


Rala And Rab8 Regulate Drosophila Embryogenesis, Zhongyuan Zuo Jan 2014

Rala And Rab8 Regulate Drosophila Embryogenesis, Zhongyuan Zuo

Electronic Theses and Dissertations

Pseudocleavage furrow dynamics initiate at cycle 10 to help with mitotic divisions that lack cytokinesis. Permanent furrows then form at the beginning of cellularization (cycle 14). Cytoskeletal networks such as F-actin and non-muscle Myosin II have been demonstrated to be required for furrow formation and provide anchor points for chromosomal segregation. However, what drives the onset of furrow formation and membrane addition remains largely unclear. In my thesis, I have explored RalA and Rab8 function during furrow formation at metaphase and cellularization stages. These furrows are critical for correct chromosomal segregation, while disruption of furrow formation results in severe developmental …


A Role For Dynamin-Dependent Endocytosis During Drosophila Gastrulation, Marissa Kay Kuhl Jan 2013

A Role For Dynamin-Dependent Endocytosis During Drosophila Gastrulation, Marissa Kay Kuhl

Electronic Theses and Dissertations

Gastrulation, a process conserved among many higher organisms, is the directed migration of cells into layers that will establish various tissues targeted to become anatomical structures. This process is accomplished through another conserved morphogenetic event, known as cell intercalation. Early in development, this movement of cells within an organized tissue leads to unique cellular arrangements where neighboring cells contract their shared interfaces in order to meet at a shared vertex. In this thesis, I present work that demonstrates a requirement for Dynamin-dependent endocytosis during these contraction events. Using quantitative analysis, I have identified varied cell behaviors during experiments which knockdown …


Estradiol Modulation Of Calcium Dynamics In Pituitary Mmq Lactotroph Cells, Monika Pauckova Jan 2012

Estradiol Modulation Of Calcium Dynamics In Pituitary Mmq Lactotroph Cells, Monika Pauckova

Electronic Theses and Dissertations

Pituitary lactotrophs are excitable cells that exhibit spontaneous, calcium influx triggering prolactin (PRL) secretion to stimulate lactation. Lactotrophs express estrogen receptors (ER) and are a well established estrogen-responsive cell system. 17B-estradiol (E2) is known to directly affect lactotrophs by increasing PRL transcription and biosynthesis, intracellular Ca2+ concentration ([Ca2+]i) and PRL secretion. This study demonstrates that the MMQ clonal cell line, isolated from the 7315a rat pituitary tumor, is a model lactotroph cell line that is E2-responsive. Spontaneous and evoked Ca2+ transients were especially sensitive to L-type channel block, but not affected by block of omega-conotoxin-GVIA-sensitive CaV channels or TTX-sensitive voltage-gated …


Neuronal Calcium Regulation And Cellular Stress In A Malignant Hyperthermia Disease Model, Jason Santiago Jan 2010

Neuronal Calcium Regulation And Cellular Stress In A Malignant Hyperthermia Disease Model, Jason Santiago

Electronic Theses and Dissertations

Calcium ions (Ca2+) are essential signaling molecules and must be carefully regulated to preserve specificity in function. One indispensible Ca2+ signaling protein is the ryanodine receptor (RyR) calcium release channel. RyR1 is essential for muscle contraction, and RyR1mutations can lead to severe muscle disorders such as malignant hyperthermia (MH). Recently, a mouse model of human MH (Y522S-RyR1) has been developed. In skeletal muscle, Y522S-RyR1 exhibits an increased sensitivity to activation resulting in Ca2+ leak, mitochondrial disorganization, and cellular stress. Although RyR1 expression is limited in the brain, the cerebellum may be particularly vulnerable to this disease because RyR1 is highly …


Purinergic Receptors In The Circumvallate Papillae Of Rats, Alana Marselle Montoya Jan 2008

Purinergic Receptors In The Circumvallate Papillae Of Rats, Alana Marselle Montoya

Electronic Theses and Dissertations

P2X2 receptors and P2Y4 receptors are ATP-activated cell surface receptors that gate movement of K+, Na+, and Ca2+. We used immunocytochemistry for P2X2 and P2Y4 receptors as well as taste cell type markers to learn if P2X2 immunoreactivity (IR) is present in nerve processes in close apposition to Type II and/or Type III taste cells. We also tested to see if P2Y4 IR is present in Type II and/or Type III taste cells. Our results indicate that P2X2 is present only in intragemmal nerve processes. P2X2-LIR nerve processes form close contacts with Type II and Type III taste cells. P2Y4 …