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Full-Text Articles in Cell Biology

Identification And Characterization Of Regulators Of Glut4 Trafficking, Daniel Richard Gulbranson Feb 2018

Identification And Characterization Of Regulators Of Glut4 Trafficking, Daniel Richard Gulbranson

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Cargo proteins moving between organelles are transported by membrane-enclosed vesicles. Identifying the factors regulating vesicle-mediated transport remains a major challenge in mammalian cells. Here, we performed unbiased genome-wide CRISPR-Cas9 genetic screens to systematically dissect insulin-dependent translocation of glucose transporters (GLUTs), a classic vesicle transport pathway crucial to mammalian physiology. These screens identified known regulators of the pathway as well as a large number of unknown regulatory factors that we validated in secondary screens. The identified genes encode established or predicted factors involved in vesicle budding or fusion, cargo sorting, signal transduction, cell motility, and cellular metabolism, as well as proteins ...


Targets And Functions Of The Microrna-200 Family In The Developing Skin And Hair Follicle, Jaimee Elizabeth Hoefert Jan 2018

Targets And Functions Of The Microrna-200 Family In The Developing Skin And Hair Follicle, Jaimee Elizabeth Hoefert

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The microRNA-200 (miR-200) family is well known for preventing epithelial-to-mesenchymal transition in cancer. However, the targets and functions of this family in normal epithelial tissues remain unclear. This five-member microRNA (miRNA) family also presents a unique platform for studying miRNA-mediated regulation, as they share two nearly-identical seed sequences. The results presented within this dissertation establish a role for these miRNAs in governing hair follicle morphogenesis and fine-tuning cell specification by regulating cell adhesion, polarity, and signaling pathways. By directly ligating miRNAs to their targeted mRNA regions, numerous miR-200 family targets are identified, many of which are involved ...


Novel Factors At Endoplasmic Reticulum-Endosome Contact Sites, Melissa J. Hoyer Jan 2018

Novel Factors At Endoplasmic Reticulum-Endosome Contact Sites, Melissa J. Hoyer

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The endoplasmic reticulum is the cell’s platform for protein and lipid synthesis. Not only does the ER perform these functions, but it also regulates other organelles through membrane contact sites. To better understand the functions of ER membrane contact sites (MCSs), we optimized tools to monitor contact sites and identify new proteins at these MCSs. We recently showed ER MCSs mark positions of the fission of other organelles. To define the role of ER at this unique MCS, we targeted a promiscuous biotin ligase to the endosome budding domains that form from the endosome body and undergo fission from ...


Tissue Retention Of Norrin: A Ligand Required For Retinal Vascularization, Lavan Khandan Jan 2017

Tissue Retention Of Norrin: A Ligand Required For Retinal Vascularization, Lavan Khandan

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The Norrin ligand is a small (14 kDa) cystine-knot protein, required for the proper vascularization of retinal, cerebellar and inner ear neural tissue. Both inherited human disorders and murine genetic studies implicate Norrin mutations in major ocular and visual defects, including retinal hypovascularization. In this thesis, I describe the property of Norrin enrichment at specific layers in the retina. I address the question of whether proper Norrin distribution in retinal tissue is required for vascularization. To do so, I used ex vivo ligand in-situ staining to interrogate differences amongst vertebrate Norrin orthologues in retinal tissue retention. I then used sequence ...


Elucidating The Ligand-Specific Role Of Tetraspanin12 As An Essential Co-Activator In Norrin/Frizzled4 Signaling And Retinal Vascularization, Maria B. Lai Jan 2017

Elucidating The Ligand-Specific Role Of Tetraspanin12 As An Essential Co-Activator In Norrin/Frizzled4 Signaling And Retinal Vascularization, Maria B. Lai

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Genetic evidence indicates that specific combinations of accessory proteins and ligands mediate vascular Frizzled (FZD) signaling via beta-catenin in different CNS structures. Accessory proteins in FZD receptor complexes are thought to determine ligand-selectivity and signaling amplitude. In the retina, TSPAN12 is an essential co-activator in Norrin/FZD4 signaling to mediate angiogenesis. The genes encoding mediators of Norrin/FZD4 signaling are linked to familial exudative vitreoretinopathy (FEVR), an inherited retinal disease that can lead to blindness. Yet, the molecular function of TSPAN12 and the specific cell type in which TSPAN12 functions in the retina remains poorly understood. Here, I utilized binding ...


Identification And Characterization Of Regulators Of Glut4 Trafficking, Daniel Richard Gulbranson Jan 2017

Identification And Characterization Of Regulators Of Glut4 Trafficking, Daniel Richard Gulbranson

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Cargo proteins moving between organelles are transported by membrane-enclosed vesicles. Identifying the factors regulating vesicle-mediated transport remains a major challenge in mammalian cells. Here, we performed unbiased genome-wide CRISPR-Cas9 genetic screens to systematically dissect insulin-dependent translocation of glucose transporters (GLUTs), a classic vesicle transport pathway crucial to mammalian physiology. These screens identified known regulators of the pathway as well as a large number of unknown regulatory factors that we validated in secondary screens. The identified genes encode established or predicted factors involved in vesicle budding or fusion, cargo sorting, signal transduction, cell motility, and cellular metabolism, as well as proteins ...


Analysis Of Two Centrin-Binding Proteins, Poc5 And Sfr1, In Tetrahymena Thermophila Basal Bodies, Westley Heydeck Jan 2016

Analysis Of Two Centrin-Binding Proteins, Poc5 And Sfr1, In Tetrahymena Thermophila Basal Bodies, Westley Heydeck

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Basal bodies are microtubule-based structures which template, anchor, and orient cilia at the cell surface. Although basal bodies contribute to vital cell functions, the molecular contributors of their assembly and maintenance are poorly understood. Previous studies in Tetrahymena thermophila revealed important roles for centrins in basal body assembly, separation of new basal bodies, and stability. Here, I characterized the basal body function of two centrin-binding proteins, Sfr1 and Poc5, in Tetrahymena. Sfr1 is the only centrin-binding protein in Tetrahymena that localizes to all cortical row and oral apparatus basal bodies. Poc5, on the other hand, transiently localizes to basal bodies ...


Polyomavirus Interactions With Host Cell Surface Receptors Mediate Important Steps In Virus Infection: From Signaling To Pathogenesis, Samantha D. O'Hara Jan 2016

Polyomavirus Interactions With Host Cell Surface Receptors Mediate Important Steps In Virus Infection: From Signaling To Pathogenesis, Samantha D. O'Hara

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Virus binding to the cell surface triggers an array of host responses important for infection. Gangliosides are the cell surface receptors for Polyomavirus (PyV) infection. Specificity is determined by recognition of carbohydrate moieties on the ganglioside by the major viral capsid protein VP1 and alterations in ganglioside binding cause dramatic changes in virus tropism and pathogenesis. Knockout mice lacking complex gangliosides are completely resistant to Mouse Polyomavirus (MuPyV) infection. Fibroblasts (MEFs) from these mice are likewise resistant to infection, and supplementation with specific gangliosides: GD1a, GT1b, and GT1a rescues infection. MuPyV also binds a protein receptor α4-integrin and loss of ...


Investigating The Molecular Mechanisms And Functions Of The Musashi-2 Rna-Binding Protein, Christopher Bennett Jan 2016

Investigating The Molecular Mechanisms And Functions Of The Musashi-2 Rna-Binding Protein, Christopher Bennett

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The Musashi (Msi) family of RNA-binding proteins is post-transcriptional regulators of gene expression. They were discovered in 1994 as being required for Drosophila sensory organ development. Since then, Msi proteins have been found to enhance cell proliferation and maintain stem cell identities in a multitude of mammalian tissues. In addition, overexpression of Msi proteins is often observed in many types of human cancers, most prominently the widely expressed Msi family member, Musashi-2 (Msi2). Msi2 plays oncogenic roles in hematopoietic, neural, and gastrointestinal tissues. However, Msi2 has received little attention in other tissues in which it is expressed, such as in ...


Activation And Utilization Of Dna Damage Signaling By Murine Polyomavirus, Katie Heiser Jan 2016

Activation And Utilization Of Dna Damage Signaling By Murine Polyomavirus, Katie Heiser

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Nuclear replication of DNA viruses activates DNA damage repair (DDR) pathways, which may detect and inhibit viral replication. However, many DNA viruses also depend on these pathways in order to optimally replicate their genomes. I investigated the relationship between murine polyomavirus (MuPyV) and components of DDR signaling pathways including CHK1, CHK2, H2AX, ATR, ATM, RPA, MRN, and DNAPK. I found that recruitment and retention of DDR proteins at viral replication centers was independent of H2AX, as well as the viral small and middle T-antigens. Additionally, infectious virus production required ATR kinase activity, but was independent of CHK1, CHK2, or DNAPK ...


The Multiple Functions Of Efhc1 In Tetrahymena And Xenopus, Ying Zhao Jan 2015

The Multiple Functions Of Efhc1 In Tetrahymena And Xenopus, Ying Zhao

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The basal body is the microtubule-organizing center that nucleates the axoneme of the cilium. Both basal bodies and cilia are complex intracellular organelles composed of hundreds of polypeptides found throughout the eukaryotes. Different types of cilia have various and often over-lapping functions, from driving fluid flow and cellular motility, to the establishment of distinct cellular domains and morphologies, to mediating and modulating intracellular signaling involved in tissue patterning. Dysfunction of basal body or ciliary components has been implicated in a variety of human diseases. EFHC1 is conserved from single cell alga to human beings. Members of this protein family contain ...


Sexually Dimorphic Cardiac Adaptation Is Mediated By Cre Expression, Independent Of Estrogen-Receptor-Α Expression, Emily K. Pugach Jan 2015

Sexually Dimorphic Cardiac Adaptation Is Mediated By Cre Expression, Independent Of Estrogen-Receptor-Α Expression, Emily K. Pugach

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The mammalian heart is a remarkably adaptable organ. In particular, the contractile cells of the heart, the cardiac myocytes can respond to dramatic changes in metabolic and functional demand. Both clinical data and murine genetic studies suggest fundamental differences in male and female cardiac biology, including at the cellular level of the myocyte. In this thesis, I address the clinical question of why cardiovascular disease differs in males and females at the cardiac myocyte level. Specifically, I elucidate the importance and mechanism of estrogen signaling in male and female cardiac myocytes. Upon identifying Estrogen Receptor-α (ERα) as the predominant estrogen ...


Study Of Sub-Cellular Structures Upon Low-Glucose Starvation In S. Pombe, Minghua Liu Jan 2015

Study Of Sub-Cellular Structures Upon Low-Glucose Starvation In S. Pombe, Minghua Liu

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Many cells and organisms react to depletion of nutrients with an energy saving program. Here we studied Schizosaccharomyces pombe (S. pombe; fission yeast) cells and how they respond to nutrient starvation by entering a quiescent state that is characterized by a substantial viscosity increase of the cytoplasm, which we term "cytoplasmic freezing". Recently we found evidence that the transition in viscosity of the cell cytoplasm could be reliably reproduced by starving S. pombe cells of glucose. Also, there is evidence that septins, a GTP binding protein family, might be involved in generating and maintaining the frozen cytoplasmic state. Here I ...


Dissecting Membrane Trafficking In The Genomic Era: Components And Molecular Mechanisms, Eric Michael Davis Jan 2015

Dissecting Membrane Trafficking In The Genomic Era: Components And Molecular Mechanisms, Eric Michael Davis

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Forward genetics in classic model organisms has been a key driving force for establishing the basic principles of cellular biology. However, many cellular pathways including membrane trafficking pathways are more complex in mammals, often exhibiting unique features not found in lower model organisms. To address this, I use a multi-pronged approach taking advantage of the haploid genetic system in human cells to explore these genetic features in a mammalian cell context. First, I direct a series of forward comparative genetic screens toward the dissection of a class of membrane bound molecules -the glycophosphatidylinositol-anchored proteins (GPI- APs). My findings demonstrate that ...


A New Role For The Endoplasmic Reticulum At Endosome Contact Sites, Ashley Ann Rowland Jan 2015

A New Role For The Endoplasmic Reticulum At Endosome Contact Sites, Ashley Ann Rowland

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The Endoplasmic Reticulum (ER) forms a dynamic network that spans throughout the cell. In addition to the well characterized roles in lipid synthesis, protein folding, and calcium handling, the ER coordinates important functions at stable membrane contact sites formed with other organelles. Recent work from the lab demonstrated that ER tubules circumscribe mitochondrial constrictions and define the position of mitochondrial fission. We predicted that mechanisms of membrane fission are conserved between various organelles. Here we hypothesized and tested whether ER contacts define the timing and the position of endosome fission. Endocytic cargo and Rab GTPases are segregated to distinct domains ...


Identification Of Novel Microrna Targets And Tumor Suppressive Functions Of Mir-203 In Murine Skin, Kent Augustus Riemondy Jr. Jan 2015

Identification Of Novel Microrna Targets And Tumor Suppressive Functions Of Mir-203 In Murine Skin, Kent Augustus Riemondy Jr.

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

miRNAs are small non-coding RNAs, approximately 22 nucleotide in length, that mediate post-transcriptional repression of target mRNAs. Since their discovery in mammals in the early 2000s, miRNAs have been intensely studied and determined to be an important mechanism to regulate gene expression in diverse biological processes. In human cancers, miRNAs are known to act as tumor suppressors or oncogenes and are being actively explored as a possible mechanism for therapeutic intervention. In the mouse, multistage skin carcinogenesis is a well-established model for studying tumor development however the functions of miRNAs in this model are poorly understood.

The Ras oncogene was ...


Examining Post-Transcriptional Regulation Of Skeletal Muscle Satellite Cell Homeostasis, Activation And Fate Determination, Crystal Dawn Pulliam Jan 2014

Examining Post-Transcriptional Regulation Of Skeletal Muscle Satellite Cell Homeostasis, Activation And Fate Determination, Crystal Dawn Pulliam

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Skeletal muscle is essential for respiration, mobility, reproduction and metabolism. Deficits in muscle function due to disease, injury or age reduce both quality of life and lifespan. Muscles are long-lived tissues that require maintenance to retain functional integrity throughout the life of an organism. Satellite cells are the adult stem cells responsible for muscle repair and maintenance. Upon myotrauma, satellite cells re-enter the cell cycle, proliferate, and terminally differentiate to repair the muscle. In uninjured tissue, satellite cells are quiescent and infrequently proceed through myogenesis for muscle maintenance. The molecular mechanisms that regulate satellite cell quiescence and activation are poorly ...


Characterization Of Microrna Function During Skeletal Myogenesis, Martin G. Guess Jan 2014

Characterization Of Microrna Function During Skeletal Myogenesis, Martin G. Guess

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Skeletal muscle is a remarkable organ system that is required for almost all animal life. In vertebrates, skeletal muscle can alter its functional and molecular characteristics in response to pathologic and physiologic stimuli. Additionally, adult muscle retains the ability to regenerate following injury, activating progenitor cells much like the process of muscle formation during embryonic development. Much work has been done to characterize the changes in gene expression that occur during regeneration, and this knowledge has been invaluable in treatment of muscle wasting diseases, such as Duchenne Muscular Dystrophy. Further expanding the complexity of gene expression changes is the discovery ...


Phosphoregulation Of Sfi1 Is Required For Yeast Centrosome Duplication And Separation, Jennifer Susan Avena Jan 2014

Phosphoregulation Of Sfi1 Is Required For Yeast Centrosome Duplication And Separation, Jennifer Susan Avena

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Centrosomes serve as the main microtubule–organizing centers in many eukaryotic cells. Duplication of centrosomes once per cell cycle is essential for bipolar spindle formation and genome maintenance and requires control by protein kinases, including cyclin–dependent kinases (Cdks). However, an understanding of the mechanisms by which centrosome duplication is regulated and, in particular, restricted to once per cell cycle is still lacking. Sfi1, a conserved component of centrosomes, is a phospho–protein that is a key candidate for establishing the site of new centrosome assembly in the budding yeast Saccharomyces cerevisiae, likely via domain–specific functions. I have examined ...


Using Computational Models To Assess The Functional Consequences Of Bdnf-Induced Excitatory And Inhibitory Synapse Formation, Domenico Fortunato Galati Jan 2013

Using Computational Models To Assess The Functional Consequences Of Bdnf-Induced Excitatory And Inhibitory Synapse Formation, Domenico Fortunato Galati

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The action potential is fundamental to the transfer of information between neurons. The generation of an action potential is influenced by the spatial distribution of dendrites and synapses around the neuronal soma where the action potential is initiated. Brain-derived neurotrophic factor (BDNF) is a secreted molecule that influences synapse density and action potential generation. In this thesis, I test the hypothesis that elevated BDNF signaling increases the rate of action potential generation by promoting a spatial distribution of synapses that is more efficient at generating action potentials. I begin by developing an algorithmic approach for constraining computational models of action ...


The Guanine Nucleotide Exchange Factors Vps9 And Mon1-Ccz1 Coordinate Endosome Maturation In Saccharomyces Cerevisiae, Therese Shideler Jan 2013

The Guanine Nucleotide Exchange Factors Vps9 And Mon1-Ccz1 Coordinate Endosome Maturation In Saccharomyces Cerevisiae, Therese Shideler

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Transmembrane proteins at the plasma membrane that are targeted for degradation in the lysosome are sorted through the endosomal pathway. At endosomes they are sorted into inward budding intralumenal vesicles (ILVs) through the concerted action of the endosomal sorting complexes required for transport (ESCRTs). Deletion of ESCRT genes in S. cerevisiae disrupts endosomal morphology leading to aberrant flattened stacks of endosomal membranes known as class E compartments. Recently we have shown that class E compartments form due to hyperactivation of the Rab5 homolog, Vps21, as well as failure to activate the Rab7 homolog, Ypt7. Here we show that class E ...


Dysregulated Fgf And P38 Mapk Signaling Underlies Loss Of Stem Cell Self-Renewal In Aging Skeletal Muscle, Jennifer Delaney Bernet Jan 2013

Dysregulated Fgf And P38 Mapk Signaling Underlies Loss Of Stem Cell Self-Renewal In Aging Skeletal Muscle, Jennifer Delaney Bernet

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Sarcopenia is a geriatric syndrome characterized by loss of skeletal muscle mass, skeletal muscle function and decreased regenerative capacity. A number of skeletal muscle-specific physiological decrements may contribute to sarcopenia; among these is an age-related impairment of satellite cells, the skeletal muscle stem cells required for muscle regeneration. I find that cell-autonomous deficits underlie a loss of self-renewal in aging satellite cells. The decline in self-renewal implicates altered p38αβ mitogen-activated protein kinase (MAPK) activity, which is activated by fibroblast growth factor (FGF) signaling and involved in satellite cell activation, differentiation and self-renewal in young satellite cells. Asymmetric activation of active ...


The Function Of Centralspindlin In Drosophila Development, Michael Craig Sfregola Jan 2013

The Function Of Centralspindlin In Drosophila Development, Michael Craig Sfregola

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Centralspindlin is an essential protein complex in all metazoans well-studied for its essential role in cytokinesis. Emerging evidence suggests centralspindlin has important interphase functions as well. Through its regulation of Rho family small GTPases at the plasma membrane, the centralspindlin complex is able to effect a number of cellular process including cell adhesion and cell migration. In this thesis I explored centralspindlin's function in development and tissue morphogenesis. In addition I investigated potential nuclear functions of the centralspindlin complex. To address these potential functions of centralspindlin I used the model organism Drosophila melanogaster.

I found centralspindlin is essential for ...


Catalysis Of Neurotransmitter Release Is A Target Of Alzheimer’S Disease: Etiologic Mechanism And Novel Therapeutic Potential, Daniel Jack Adams Jan 2013

Catalysis Of Neurotransmitter Release Is A Target Of Alzheimer’S Disease: Etiologic Mechanism And Novel Therapeutic Potential, Daniel Jack Adams

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Alzheimer's disease is a devastating neurodegenerative syndrome that afflicts tens of millions of patients worldwide for which no effective therapy or prevention currently exists. Although the disease mechanisms remain elusive, it is clear that the 42 amino acid β-amyloid peptide is of central importance. The present work has combined structural, biochemical and in vivo analyses to uncover a catalytic role for the major synaptic vesicle protein synaptophysin in neurotransmitter release. We have found that this catalytic activity is directly targeted and inhibited by the beta-amyloid peptide causing synaptic dysfunction early in the progression of Alzheimer's disease. The novel ...


Determining The Role Of Wnt Signaling During Bdnf-Induced Cortical Neuron Growth And Dendritic Spine Formation, Brian Gibson Hiester Jan 2012

Determining The Role Of Wnt Signaling During Bdnf-Induced Cortical Neuron Growth And Dendritic Spine Formation, Brian Gibson Hiester

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Dendritic spines are major sites of excitatory synaptic transmission and changes in their densities and morphologies have been linked to neurodevelopmental disorders and neurodegenerative diseases. The Jones lab has previously shown using a forebrain-specific BDNF knockout mouse (fsBDNF-KO) that loss of BDNF leads to a significant reduction in dendritic spine density and a loss of dendrites in cortical neurons. However, the mechanisms by which BDNF regulates dendrites and dendritic spine formation remain unclear. I propose that one mechanism by which BDNF regulates these processes is by controlling the expression of other secreted signaling proteins, thereby establishing bidirectional communication between neurons ...


Paternal Mitochondria Elimination And Cell Death Regulation In C. Elegans, Qinghua Zhou Jan 2012

Paternal Mitochondria Elimination And Cell Death Regulation In C. Elegans, Qinghua Zhou

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The nematode C. elegans is a model organism for various biomedical studies due to its genetic simplicity and conservation with humans. As C. elegans is uniquely amenable to cellular, molecular genetic, and biochemical analyses, many basic biological processes are investigated by experimentally manipulating and observing worms. My thesis describes how I used C. elegans models to advance our understanding of paternal mitochondria elimination and cell death regulation.

Mitochondria are membrane-enclosed organelles that carry their own genome (mtDNA). In mammals, the inheritance of mitochondria and mtDNA is strictly maternal, despite the fact that a sperm can inject up to 100 functional ...


Ε-Tubulin And Δ-Tubulin In Tetrahymena Thermophila Are Essential Components Of Basal Bodies, Ian Ross Jan 2012

Ε-Tubulin And Δ-Tubulin In Tetrahymena Thermophila Are Essential Components Of Basal Bodies, Ian Ross

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Basal bodies and centrioles are conserved microtubule-based organelles whose improper assembly leads to a number of diseases, including ciliopathies, such as polycystic kidney disease and Bardet-Biedl syndrome, and cancer. Tubulin family members are conserved components of these structures that are integral to their proper formation and function. The nine-fold triplet microtubule organization of basal bodies is a widely conserved structural feature. Two proteins that have been implicated in the proper assembly and maintenance of this structure are ε- and δ-tubulin. I sought to ask what the functions of these two proteins are in the assembly and maintenance of the core ...


Novel Molecular Mechanisms That Modulate The Cellular Response To P53 Activation, Ryan Edward Henry Jan 2012

Novel Molecular Mechanisms That Modulate The Cellular Response To P53 Activation, Ryan Edward Henry

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The p53 tumor suppressor protein is the most frequently mutated gene in human tumors and is amongst the most intensely studied molecules in modern biology. p53 acts primarily as a stress-responsive transcription factor that directly regulates the expression of over one hundred target genes, the products of which mediate such tumor suppressive responses as cell cycle arrest, apoptosis, senescence and DNA damage repair. It is well established that p53-dependent cellular stress responses can vary, depending on both the nature of the p53-activating stimulus as well as the cell type experiencing the stress; however, the molecular mechanisms that drive cells to ...


The Drosophila Receptor Tyrosine Kinase Tie Instructs Function Of The Bantam Microrna In The Response To Ionizing Radiation, Amber Bilak Jan 2012

The Drosophila Receptor Tyrosine Kinase Tie Instructs Function Of The Bantam Microrna In The Response To Ionizing Radiation, Amber Bilak

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Life or death choices of cells in Drosophila depend on the accumulation of critical levels of pro-apoptotic factors such as hid. Ionizing radiation (IR) causes lesions to macromolecules in cells that trigger damage responses and result in death of cells expressing critical amounts of hid. Cells are eliminated by apoptosis to prevent the transfer of damaged genetic material to daughter cells. However, some cells must be preserved in order for organisms to survive and regenerate. Therefore, genes that limit apoptosis can enhance organismal survival. The ban miRNA limits apoptosis after IR exposure by regulating the 3'UTR of hid. Though ...


Rab10 Gtpase Regulates Er Dynamics And Morphology, Amber English Jan 2012

Rab10 Gtpase Regulates Er Dynamics And Morphology, Amber English

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

I have identified Rab10 as an ER specific Rab GTPase that regulates ER structure and dynamics. I show that Rab10 localizes to the ER and to dynamic ER-associated structures that track along microtubules and mark the position of new ER tubule growth. Rab10 depletion or expression of a Rab10 GDP-locked mutant alters ER morphology, resulting in a decrease in ER tubules. I demonstrate that this defect is due to a reduced ability of dynamic ER tubules to grow out and successfully fuse with adjacent ER. Consistent with this function, Rab10 partitions to dynamic ER-associated domains found at the leading edge ...