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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 ...


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 ...


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 ...


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 ...


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 ...


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 ...


An Asymmetric Jam2/Par Complex Renews Muscle Stem Cells By Localized P38alpha/Beta Mapk Signaling, Andrew A. Troy Jan 2011

An Asymmetric Jam2/Par Complex Renews Muscle Stem Cells By Localized P38alpha/Beta Mapk Signaling, Andrew A. Troy

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Skeletal muscle is maintained and repaired by satellite cells. Satellite cells are quiescent in uninjured muscle but activate, proliferate and repair the muscle after injury. The quiescent satellite cell population is renewed during the injury repair, but how and when this happens is unclear. Recently, several subpopulations of satellite cells have been described with an enhanced capacity for self-renewal raising the possibility that there is a subset of satellite cells dedicated to maintaining the quiescent satellite cell population. I find that all satellite cells activate in response to injury and, after the first division, quiescent satellite cells reappear. I show ...


Regulation Of Escrt-Iii Assembly And Membrane Scission Activity In The Budding Yeast Saccharomyces Cerevisiae, Megan Anne Wemmer Jan 2011

Regulation Of Escrt-Iii Assembly And Membrane Scission Activity In The Budding Yeast Saccharomyces Cerevisiae, Megan Anne Wemmer

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The sequential recruitment and assembly of endosomal sorting complexes required for transport (ESCRTs) at the endosomal membrane mediate the selection and clustering of cargoes into vesicles that bud into the lumen of the endosome. In addition to regulating this sorting process at endosomes, in mammalian cells ESCRTs are additionally required for the budding of many types of enveloped viruses, as well as the separation of cells during cytokinesis. These processes share a topologically similar membrane scission event facilitated by regulated ESCRT-III assembly at the cytoplasmic surface of the membrane to promote the formation and scission of internal vesicles. The Snf7 ...


How Reticulon Gets The Er Into Shape, Nesia A. Zurek Jan 2011

How Reticulon Gets The Er Into Shape, Nesia A. Zurek

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The endoplasmic reticulum (ER) is an organelle that extends throughout the cell cytoplasm and has a complex membrane structure. There are three major ER domains, the nuclear envelope, the ER cisternae, and the tubular ER. Each domain is structured by its own set of membrane shaping proteins. The protein family that is the focus of this study is the reticulons. The reticulons generate curvature throughout the ER, specifically at the tubular ER and the edges of ER cisternae. All reticulons tested partition exclusively to high curvature ER and generate immobile oligomers. Every reticulon contains the reticulon homology domain (RHD) at ...


Cardiac Atrophy Due To Cancer: Characterization, Mechanisms, And Sex Differences, Pippa Froukje Cosper Jan 2011

Cardiac Atrophy Due To Cancer: Characterization, Mechanisms, And Sex Differences, Pippa Froukje Cosper

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Approximately one-third of cancer deaths are caused by cachexia, a severe form of skeletal muscle and adipose tissue wasting that affects men more than women. The heart also undergoes atrophy in cancer patients but the extent, functional consequences, mechanisms and sex differences have not been elucidated. In a mouse colon-adenocarcinoma model, cancer causes a loss of cardiac mass due to a decrease in cardiac myocyte size that is associated with reduced levels of all sarcomeric proteins. I provide evidence that published reports showing a selective decrease in myosin heavy chain (MyHC) during cancer cachexia are likely an artifact resulting from ...


Investigating The Components And Assembly Of Processing Bodies In Human Cells, Jaclyn Rose Dennis Jan 2011

Investigating The Components And Assembly Of Processing Bodies In Human Cells, Jaclyn Rose Dennis

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Messenger RNA degradation is important for the control of gene expression. The major mRNA decay pathway requires the coordination of proteins involved in deadenylation, decapping, and exonucleolysis to function properly. Interestingly, many of those proteins, as well as translationally repressed mRNAs, localize to discreet cytoplasmic foci called processing bodies (PBs). It remains unclear how PBs form and their functional significance is, as yet, unknown. To better understand how PB assembly may be regulated, I tested whether the cytoskeleton is required for PB dynamics in human cells. I found that the cytoskeleton is likely not required for overall PB assembly, integrity ...


An Analysis Of Latent Membrane Protein-1 Signaling Complexes And Their Contribution To Epstein-Barr Virus Infection, Ryan Akira Takeshita Jan 2011

An Analysis Of Latent Membrane Protein-1 Signaling Complexes And Their Contribution To Epstein-Barr Virus Infection, Ryan Akira Takeshita

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

In immunocompromised individuals, B cells infected with Epstein-Barr virus often display tumorigenic growth. One of the viral oncoproteins that contributes to this transformation is the latent membrane protein-1 (LMP-1), which constitutively mimics the signaling of ligand-dependent CD40, a tumor necrosis factor receptor. The experiments described in this dissertation were designed to elucidate the molecular mechanisms that underlie LMP-1's signaling potential. We investigated the relationships between LMP-1's subcellular localization, homo-oligomerization, comigration with detergent-resistant membranes, and its signaling outputs in order to bridge some of the gaps standing in the way of a unified theory of LMP-1 function. The data ...