Open Access. Powered by Scholars. Published by Universities.®

Cell Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

2014

Discipline
Institution
Keyword
Publication
Publication Type
File Type

Articles 331 - 360 of 365

Full-Text Articles in Cell Biology

T Cells Bearing A Chimeric Antigen Receptor Against The Tumor Vasculature Destroy The Tumor Endothelium And Result In Tumor Regression, Stephen Santoro Jan 2014

T Cells Bearing A Chimeric Antigen Receptor Against The Tumor Vasculature Destroy The Tumor Endothelium And Result In Tumor Regression, Stephen Santoro

Publicly Accessible Penn Dissertations

Aberrant blood vessels enable tumor growth, provide a barrier to immune infiltration, and serve as a source of pro-tumorigenic signals. Targeting tumor blood vessels for destruction, or tumor vascular disruption therapy, can therefore provide significant therapeutic benefit. Here I describe the development of two chimeric antigen receptors (CAR)s against the tumor vasculature, targeting either tumor endothelial marker 1 (TEM1) or prostate-specific membrane antigen (PSMA). CAR T cells incorporating scFv78, an scFv isolated against TEM1, were able to recognize immobilized plate-bound TEM1 protein, but were unable to recognize TEM1 on the surface of endothelial cell targets. In contrast, anti-PSMA CAR ...


A Structure-Function Analysis Of The Arabidopsis Chloroplast Import Protein Attic20, James H. Campbell Jan 2014

A Structure-Function Analysis Of The Arabidopsis Chloroplast Import Protein Attic20, James H. Campbell

Theses and Dissertations (Comprehensive)

Arabidopsis thaliana protein Tic20 (atTic20) is a member of the translocon at the inner envelope membrane of chloroplasts. Evidence to date suggests it is part of the main preprotein conducting aperture in the complex, but its exact role is still debated. To help characterize its role, a protocol optimizing yield and purity of recombinantly expressed atTic20 was developed, and a series of experiments was performed to examine its secondary structure and its ability to interact with chloroplast transit peptides. The attempt to increase protein yield was successful, with growth at 20oC in the auto-inducing media ZYP-5052 showing the ...


Characterizing Dsrna Production In Virus-Infected Fish Cells, Amal Brek Aloufi Jan 2014

Characterizing Dsrna Production In Virus-Infected Fish Cells, Amal Brek Aloufi

Theses and Dissertations (Comprehensive)

Viral dsRNA is produced by almost all viruses sometime during their replicative cycle. These viral nucleic acids are potent inducers of both innate and adaptive immune responses, and are therefore considered important immuno-modulators. Previous studies have shown that viruses produce dsRNA when replicating in mammalian cells; however, to date no one has demonstrated viral dsRNA production in virus infected fish cells. Therefore, the goal of this study is to investigate dsRNA production by fish viruses in fish cells, verifying production and performing initial characterization of the dsRNA molecules being produced. Three different rainbow trout cell lines were used in this ...


Allosteric Regulation Of The Hsp90 Dynamics And Stability By Client Recruiter Cochaperones: Protein Structure Network Modeling, Kristin Blacklock, Gennady M. Verkhivker Jan 2014

Allosteric Regulation Of The Hsp90 Dynamics And Stability By Client Recruiter Cochaperones: Protein Structure Network Modeling, Kristin Blacklock, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

The fundamental role of the Hsp90 chaperone in supporting functional activity of diverse protein clients is anchored by specific cochaperones. A family of immune sensing client proteins is delivered to the Hsp90 system with the aid of cochaperones Sgt1 and Rar1 that act cooperatively with Hsp90 to form allosterically regulated dynamic complexes. In this work, functional dynamics and protein structure network modeling are combined to dissect molecular mechanisms of Hsp90 regulation by the client recruiter cochaperones. Dynamic signatures of the Hsp90-cochaperone complexes are manifested in differential modulation of the conformational mobility in the Hsp90 lid motif. Consistent with the experiments ...


Computational Modeling Of Allosteric Regulation In The Hsp90 Chaperones: A Statistical Ensemble Analysis Of Protein Structure Networks And Allosteric Communications, Kristin Blacklock, Gennady M. Verkhivker Jan 2014

Computational Modeling Of Allosteric Regulation In The Hsp90 Chaperones: A Statistical Ensemble Analysis Of Protein Structure Networks And Allosteric Communications, Kristin Blacklock, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

A fundamental role of the Hsp90 chaperone in regulating functional activity of diverse protein clients is essential for the integrity of signaling networks. In this work we have combined biophysical simulations of the Hsp90 crystal structures with the protein structure network analysis to characterize the statistical ensemble of allosteric interaction networks and communication pathways in the Hsp90 chaperones. We have found that principal structurally stable communities could be preserved during dynamic changes in the conformational ensemble. The dominant contribution of the inter-domain rigidity to the interaction networks has emerged as a common factor responsible for the thermodynamic stability of the ...


The Establishment Of A Fibroblastic Cell Line From Yellow Perch (Perca Flavescens) And Its Potential Applications In Toxicology, Katelin W. Spiteri Jan 2014

The Establishment Of A Fibroblastic Cell Line From Yellow Perch (Perca Flavescens) And Its Potential Applications In Toxicology, Katelin W. Spiteri

Theses and Dissertations (Comprehensive)

This thesis describes the establishment, characterization and potential toxicological applications of YPF5, a yellow perch cell line. YPF5 is a fibroblastic cell line derived from the caudal fin of yellow perch. This cell line has been maintained for over 2 years. Cultures have been passaged over 60 times, and successfully cryopreserved and thawed. YPF5 is grown at room temperature in Leibovitz-15 (L-15) media, supplemented with 10% fetal bovine serum and 3% penicillin-streptomycin. The origin of YPF5 has been confirmed as Perca flavescens through “DNA Barcoding” and reaffirmed through Karyotyping (2n = 48) as per literature reported karyology for percidae including the ...


Rapid Method Of Processing Sperm For Nucleic Acid Extraction In Clinical Research, Matthew K. De Gannes Jan 2014

Rapid Method Of Processing Sperm For Nucleic Acid Extraction In Clinical Research, Matthew K. De Gannes

Masters Theses

Background: Sperm contain highly compact nuclei, inhibiting DNA extraction using traditional techniques. Current methods extracting sperm DNA involve lengthy lysis and no means of stabilizing DNA, hindering clinical research.

Objective: We sought to optimize an efficient method of extracting high quality human sperm DNA.

Methods: Sperm from three volunteers were isolated using PureCeption. We tested 1) proteinase K with DNA/RNA Shield, 2) DTT and TCEP as reducing agents, 3) QIAshredder homogenization, and 4) stability of sperm DNA fresh (baseline) or after 4 weeks of storage at 4OC in DNA/RNA Shield using modified Quick-gDNA MiniPrep. DNA was ...


Clinical Features And Outcome Of Sporadic Colorectal Carcinoma In Young Patients: A Cross-Sectional Analysis From A Developing Country, Muhammad Nauman Zahir, Eisha Mahpara Azhar, Sobia Rafiq, Kulsoom Ghias, Munira Shabbir-Moosajee Jan 2014

Clinical Features And Outcome Of Sporadic Colorectal Carcinoma In Young Patients: A Cross-Sectional Analysis From A Developing Country, Muhammad Nauman Zahir, Eisha Mahpara Azhar, Sobia Rafiq, Kulsoom Ghias, Munira Shabbir-Moosajee

Department of Biological & Biomedical Sciences

Background: Early onset colorectal carcinoma (CRC) is rare and has been hypothesized to be a biologically and clinically distinct entity personifying aggressive disease and worse survival.
Methods: Data for 131 patients was collected by retrospective chart review. Cox proportional hazard model was used to compute prevalence ratios and 95% confidence intervals.
Results: Early onset sporadic CRC accounted for 32% of all CRC treated in the specified time period. The mean age was 33.3 ± 7.9 years and the male to female ratio was 2 : 1. Colon and rectal cancers accounted for 55% and 45% of patients, respectively. 96% of ...


The Role Of The Novel Lupus Antigen, Acheron, In Moderating Life And Death Decisions, Ankur Sheel Jan 2014

The Role Of The Novel Lupus Antigen, Acheron, In Moderating Life And Death Decisions, Ankur Sheel

Masters Theses

Programmed cell death (PCD) is a major regulatory mechanism employed during development and homeostasis. The term PCD was coined to describe the death of the intersegmental muscles (ISMs) of moths at the end of metamorphosis. The timing of ISM death in the Tobacco Hawkmoth, Manduca sexta, is regulated by a fall in the titer of the steroid molting hormone 20-hydroxyecdysone (20E) late on day 17of pupal-adult development. This triggers the release of the peptide hormone, Eclosion Hormone (EH), which mediates its effects via the secondary messenger cGMP. It has been previously demonstrated that ISM death requires de novo gene expression ...


Degradation Of The Oncoprotein Mdmx In Neurodegenerative States: Evidence For A Pro-Survival Role Of Mdmx In Neurons, Daniel James Colacurcio Jan 2014

Degradation Of The Oncoprotein Mdmx In Neurodegenerative States: Evidence For A Pro-Survival Role Of Mdmx In Neurons, Daniel James Colacurcio

Publicly Accessible Penn Dissertations

Neurodegenerative diseases, such as Alzheimer Disease (AD) and HIV–associated neurocognitive disorder (HAND) represent a tremendous burden to healthcare and a devastating impact on society. A common feature of neurodegenerative diseases is progressive dysfunction and death of neurons in key regions of the brain. Observations of dysregulated cell cycle proteins in the brains of patients, along with research in animal models and cultured cells, suggest that aberrant functions of cell cycle proteins contribute to neuronal death and progression of neurodegenerative diseases.

The p53 tumor suppressor is a key component in cell cycle signaling and cell death. p53 maintains multiple functions ...


Distinct Patterns Of Ccr5 Versus Alternative Coreceptor Dependence In Non-Natural Host Versus Natural Host Simmian Immunodeficiency Virus Infection, Sarah Tc Elliott Jan 2014

Distinct Patterns Of Ccr5 Versus Alternative Coreceptor Dependence In Non-Natural Host Versus Natural Host Simmian Immunodeficiency Virus Infection, Sarah Tc Elliott

Publicly Accessible Penn Dissertations

Natural host sooty mangabeys infected with simian immunodeficiency viruses (SIV) exhibit high plasma viral loads without widespread CD4+ T cell loss. By contrast, non-natural host rhesus macaques experimentally infected with related SIV exhibit high viral loads but display subsequent CD4+ T cell loss and progression to AIDS, analogous to the effects of HIV-1 infection in humans. Several mechanisms have been proposed to explain these discrepant outcomes, including infection of distinct target cells in vivo. Cell targeting is substantially determined at the level of viral entry. Prior work demonstrated that sooty mangabey infection occurs in the absence of functional coreceptor CCR5 ...


Mechanochemical Control Of Stem Cell Biology In Development And Disease: Experimental And Theoretical Models, Polimyr Caesar Dave Pelisco Dingal Jan 2014

Mechanochemical Control Of Stem Cell Biology In Development And Disease: Experimental And Theoretical Models, Polimyr Caesar Dave Pelisco Dingal

Publicly Accessible Penn Dissertations

Whether a stem cell remains or egresses away from its physiological niche is a function of mechanical and soluble factors in a time-dependent manner, which implicates a `memory' of prior mechanochemical conditioning. Virtually every organ in the body contains resident stem or progenitor cells that contribute to organ homeostasis or repair. The wound healing process in higher vertebrate animals is spatiotemporally complex and usually leads to scarring. Limitations for the use of stem cells as regenerative therapy include the lack of expansion capabilities in vitro as well as materials issues that complicate traditional biochemical protocols. A minimal `scar in a ...


Epigenetic Regulation Of Progenitor Cell Commitment By Hdac3, Mudit Gupta Jan 2014

Epigenetic Regulation Of Progenitor Cell Commitment By Hdac3, Mudit Gupta

Publicly Accessible Penn Dissertations

Tissue-specific progenitor cells emerge during development to expand and differentiate into the multiple cell lineages that populate the embryo. Appropriate differentiation of these precursor cells requires coordinated expression of numerous lineage-specific genes and repression of alternative fate programs. Epigenetic regulators are enzymes capable of activating or silencing large genomic domains by altering histone modifications, DNA methylation status and chromatin organization. Although differentiating progenitor cells undergo epigenetic changes and epigenetic factors are required for appropriate cell behavior, the precise mechanism of how these proteins influence cell fate remains unclear. In this dissertation, I examine the role of histone deacetylase 3 in ...


Recirculation Of Innate Lymphocyte Subsets In The Skin, Skye Geherin Jan 2014

Recirculation Of Innate Lymphocyte Subsets In The Skin, Skye Geherin

Publicly Accessible Penn Dissertations

The trafficking of innate-like lymphocytes, such as γδ T cells and B-1 B cells, has garnered comparatively little attention from the immunological community relative to conventional T and B cells. However, recent studies have shown that innate-like cell subsets are critical for immune regulation and host defense. In this study, we use a classic ovine lymph cannulation model to describe the phenotype and function of γδ T cells migrating through the skin. We find that γδ T cells traveling in the skin-draining afferent lymph are IFN-γ- and/or IL-17-producing effector cells that express high levels of the skin- and inflammation-seeking ...


Role Of Cytoskeletal Remodeling In T Cell Receptor Signaling And Integrin Activation At The Immunological Synapse, Alexander Babich Jan 2014

Role Of Cytoskeletal Remodeling In T Cell Receptor Signaling And Integrin Activation At The Immunological Synapse, Alexander Babich

Publicly Accessible Penn Dissertations

The efficiency of an immune response critically depends on the ability of T cells to respond to antigens. Upon encountering cognate antigenic peptides on the surface of antigen-presenting cells, T cells form a specialized interface, termed the immunological synapse (IS), which serves as the site of information transfer between the cells. This contact zone is characterized by the enrichment of signaling receptors, kinases and adaptor proteins, and is the site of extensive cytoskeletal remodeling. The versatile nature and spatio-temporal regulation of signaling cascades at the IS has long been recognized but the exact mechanisms that coordinate these processes remain poorly ...


Junctional Sarcoplasmic Reticulum Protein Processing And Trafficking In Cardiac Tissue And Primary Cultured Cardiomyocytes, Naama Sleiman Jan 2014

Junctional Sarcoplasmic Reticulum Protein Processing And Trafficking In Cardiac Tissue And Primary Cultured Cardiomyocytes, Naama Sleiman

Wayne State University Dissertations

Junctional SR is an important and unique ER subdomain in the adult myocyte that releases Ca2+ through the actions of an exclusive set of resident proteins. Cardiac calsequestrin (CSQ2) undergoes two co-translational modifications: N-linked glycosylation on 316Asn, and phosphorylation by protein kinase CK2 on a cluster of 3 serines in its tail. In the heart, CSQ2 molecules undergo extensive mannose trimming by ER mannosidase(s), a posttranslational process that often regulates protein breakdown. To investigate CSQ2 protein processing in cardiomyopathy models, studies were performed to test whether CSQ2 glycan structures would be altered in heart tissue from mongrel dogs induced ...


Cxcr2 Macromolecular Complex In Pancreatic Cancer: A Potential Therapeutic Target In Tumor Growth, Shuo Wang Jan 2014

Cxcr2 Macromolecular Complex In Pancreatic Cancer: A Potential Therapeutic Target In Tumor Growth, Shuo Wang

Wayne State University Dissertations

The signaling mediated by the chemokine receptor CXC chemokine receptor 2 (CXCR2) plays an important role in promoting the progression of many cancers, including pancreatic cancer, one of the most lethal human malignancies. CXCR2 possesses a consensus PSD-95/DlgA/ZO-1 (PDZ) motif at its carboxyl termini, which might interact with potential PDZ scaffold/adaptor proteins. We have previously reported that CXCR2 PDZ motif-mediated protein interaction is an important regulator for neutrophil functions. Here, using a series of biochemical assays, we demonstrate that CXCR2 is physically coupled to its downstream effector phospholipase C-β3 (PLC-β3) that is mediated by PDZ scaffold protein ...


Epithelial Cell Shape Changes During Lung Branching Morphogenesis: The Role Of Wnt/Fzd2 Signaling In Directing New Branch Formation, Rachel S. Kadzik Jan 2014

Epithelial Cell Shape Changes During Lung Branching Morphogenesis: The Role Of Wnt/Fzd2 Signaling In Directing New Branch Formation, Rachel S. Kadzik

Publicly Accessible Penn Dissertations

Formation of the intricately branched mammalian lung requires precise coordination between the epithelium and mesenchyme over the course of development. This coordination is mediated by molecular signaling between the two tissue compartments. How these signaling pathways coordinate changes in cellular and tissue morphology to give rise to the highly ramified branched network of the lung is not well understood. In this work, I show that signaling through Frizzled 2 (Fzd2) is required for promoting changes in epithelial cell shape that lead to tissue-level changes needed for branching morphogenesis in the lung. Through analysis of both fixed lungs and live imaging ...


Membrane Forces And Key Protein Determinants Of Hematopoietic Cell Function: Lamins And Myosin-Ii In Hematopoiesis And Cd47 In Immunotherapy Of Cancer, Kyle Spinler Jan 2014

Membrane Forces And Key Protein Determinants Of Hematopoietic Cell Function: Lamins And Myosin-Ii In Hematopoiesis And Cd47 In Immunotherapy Of Cancer, Kyle Spinler

Publicly Accessible Penn Dissertations

Hematopoiesis in human bone marrow generates every second about 105 – 106 anucleated platelets and red blood cells as well as nucleated white blood cells that are capable of infiltrating distant tissues. The thesis begins in the marrow with a description of (1) nuclear membrane ‘lamina’ physicochemical properties that influence marrow-to-circulation trafficking, and proceeds to detail (2) the physicochemical roles of membrane cortex ‘myosin’ in key marrow processes of motility and division as well as platelet biogenesis and disease. The thesis finishes with (3) studies of macrophages in peripheral tissues far from the marrow and aspects of how such ...


Regulation Of Zygotic Transcription And Cell Cycle Checkpoints In Early Embryogenesis, Xiang Maomao Zhang Jan 2014

Regulation Of Zygotic Transcription And Cell Cycle Checkpoints In Early Embryogenesis, Xiang Maomao Zhang

Publicly Accessible Penn Dissertations

For many organisms, the first goal of embryogenesis is to accumulate a large cell population to accommodate gastrulation. To achieve this quickly, embryos employ specialized cell cycles called cleavages that consist of continuous rounds of DNA replication and division. Cell proliferation occurs rapidly because cleavage cycles lack the gap phases and cell cycle checkpoints found in canonical cell cycles. Further, the genetic materials required to sustain cleavage cycles are preloaded during oogenesis, aiding efficient cell cycle progression. After a constant, organism-specific number of cleavages, many metazoan embryos undergo the mid-blastula transition (MBT), which initiates extensive cell cycle remodeling. Cell cycles ...


The Role Of The Exocyst In Membrane Deformation, Cell Migration And Exocytosis, Yuting Zhao Jan 2014

The Role Of The Exocyst In Membrane Deformation, Cell Migration And Exocytosis, Yuting Zhao

Publicly Accessible Penn Dissertations

Dynamic shape changes of the plasma membrane are fundamental to many processes ranging from morphogenesis and cell migration to phagocytosis and viral propagation. In this study, I showed that Exo70, a component of the exocyst complex, induces tubular membrane invaginations towards the lumen of synthetic vesicles in vitro and generates actin-free protrusions on the surface of cells. Analyses using Exo70 mutants suggest that Exo70 generates negative membrane curvature through an oligomerization-based mechanism. The membrane-deformation function of Exo70 is likely to be independent of the other exocyst subunits. Exo70 thus represents a novel membrane-deforming protein for plasma membrane remodeling. Directional cell ...


Effects Of Altering The Peroxisomal Redox State In Models Of Degenerative Disease, Courtney Rose Giordano Jan 2014

Effects Of Altering The Peroxisomal Redox State In Models Of Degenerative Disease, Courtney Rose Giordano

Wayne State University Dissertations

Peroxisomes are important regulators of cellular redox balance and function as a signaling platform to regulate anti-aging metabolic and communication networks. In addition the organelle has emerged as a major player in maintaining cellular ROS at an optimal level. At such levels, these ROS are involved in initiation of signaling cascades and that produce an array of anti-aging and disease processes. However, as cells age over time, ROS amass within the peroxisome and elsewhere in the cell. This leads to an imbalance in oxidative homeostasis and results in compromised signaling networks. The goal of this dissertation was to treat disease ...


Characterization Of Adult Zebrafish Retinal Regeneration Following Two Different Damage Models, Jennifer Lee Thomas Jan 2014

Characterization Of Adult Zebrafish Retinal Regeneration Following Two Different Damage Models, Jennifer Lee Thomas

Wayne State University Dissertations

Unlike mammals, zebrafish can regenerate all of their retinal neurons through Müller glial cells, which respond to retinal damage by re-entering the cell cycle to create clusters of progenitor cells. The progenitors continue to proliferate as they migrate to the site of damage, where they ultimately differentiate into new retinal neurons. In contrast, Müller glia of the mammalian retina respond to injury with reactive gliosis, which if persistent, can lead to loss of Müller cell function and devastating vision loss. Despite this, multiple lines of evidence suggest that mammalian Müller glial cells possess a latent ability to regenerate retinal neurons ...


Mitochondrial Dynamics: Exploring A Novel Target Against Myocardial Ischemia-Reperfusion Injury, Yi Dong Jan 2014

Mitochondrial Dynamics: Exploring A Novel Target Against Myocardial Ischemia-Reperfusion Injury, Yi Dong

Wayne State University Dissertations

Mitochondrial fusion and fission, collectively termed mitochondrial dynamics, are among the core mechanisms responsible for maintaining mitochondrial health and functional integrity. Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission. Recent studies suggest that i) mitochondrial dynamics, particularly, mitochondrial fission, serves as a mediator of cell fate in the setting of ischemia-reperfusion (IR) injury, and, ii) inhibition of DRP1 and mitochondrial fission provides cardioprotection against IR injury. However, the precise role of DRP1 translocation to mitochondria in the pathogenesis of myocardial ischemia-reperfusion injury has not been established.

Using an established model of hypoxia-reoxygenation (HR) in cultured HL-1 cardiomyocytes ...


Regulation Of Inositol Biosynthesis And Cellular Consequences Of Inositol Depletion: Implications For The Mechanism Of Action Of Valproate, Rania M. Deranieh Jan 2014

Regulation Of Inositol Biosynthesis And Cellular Consequences Of Inositol Depletion: Implications For The Mechanism Of Action Of Valproate, Rania M. Deranieh

Wayne State University Dissertations

Inositol is a six-carbon cyclitol that is ubiquitous in biological systems. It is a precursor for the synthesis of numerous biologically important compounds, including inositol phosphates and phosphoinositides that are essential for cell function and viability. Inositol compounds play a role in membrane formation, gene regulation, signaling, regulation of ion channels, and membrane trafficking. Furthermore, inositol regulates hundreds of genes, including those involved in the biosynthesis of inositol and phospholipids. While transcriptional regulation of inositol biosynthesis has been extensively studied and well characterized, regulation of inositol biosynthesis at the enzymatic level has not been addressed. The current study shows that ...


Structure-Function Analysis Of Zapc, An Ftsz-Ring Stabilizer, In Escherichia Coli Cytokinesis, Lukasz Tchorzewski Jan 2014

Structure-Function Analysis Of Zapc, An Ftsz-Ring Stabilizer, In Escherichia Coli Cytokinesis, Lukasz Tchorzewski

Dissertations and Theses

In Escherichia coli, cell division is defined by the polymerization and constriction of a cytokinetic ring (Z ring) formed by FtsZ, a tubulin-like GTPase, at midcell. Division also involves the formation of a multi-protein complex at midcell known as the divisome. Several divisome proteins promote the assembly/disassembly processes of FtsZ, thereby exercising spatiotemporal control over division. Among FtsZ regulatory proteins are the FtsZ ringassociated proteins (Zap), which either directly or indirectly stabilize the Z-ring by increasing lateral interactions amongst FtsZ protofilaments in the Z-ring. ZapA-D are recruited during early cytokinesis and have overlapping functions in stabilizing FtsZ at midcell ...


A Conserved Flagella-Associated Protein In Chlamydomonas, Fap234, Is Essential For Axonemal Localization Of Tubulin Polyglutamylase Ttll9, Tomohiro Kubo, Haru-Aki Yanagisawa, Zhongmei Liu, Rie Shibuya, Masafumi Hirono, Ritsu Kamiya Jan 2014

A Conserved Flagella-Associated Protein In Chlamydomonas, Fap234, Is Essential For Axonemal Localization Of Tubulin Polyglutamylase Ttll9, Tomohiro Kubo, Haru-Aki Yanagisawa, Zhongmei Liu, Rie Shibuya, Masafumi Hirono, Ritsu Kamiya

University of Massachusetts Medical School Faculty Publications

Tubulin undergoes various posttranslational modifications, including polyglutamylation, which is catalyzed by enzymes belonging to the tubulin tyrosine ligase-like protein (TTLL) family. A previously isolated Chlamydomonas reinhardtii mutant, tpg1, carries a mutation in a gene encoding a homologue of mammalian TTLL9 and displays lowered motility because of decreased polyglutamylation of axonemal tubulin. Here we identify a novel tpg1-like mutant, tpg2, which carries a mutation in the gene encoding FAP234, a flagella-associated protein of unknown function. Immunoprecipitation and sucrose density gradient centrifugation experiments show that FAP234 and TTLL9 form a complex. The mutant tpg1 retains FAP234 in the cell body and flagellar ...


Mechanisms Of Cyclooxygenase-2-Dependent Human Aortic Smooth Muscle Cell Phenotypic Modulation, Oreoluwa O. Adedoyin Jan 2014

Mechanisms Of Cyclooxygenase-2-Dependent Human Aortic Smooth Muscle Cell Phenotypic Modulation, Oreoluwa O. Adedoyin

Theses and Dissertations--Pharmacy

Abdominal aortic aneurysm (AAA) is a disease of the aorta characterized by pathological remodeling and progressive weakening of the vessel resulting in the increased risk of rupture and sudden death. In a mouse model of the disease induced by chronic Angiotensin II (AngII) infusion, progression of AAAs is associated with reduced differentiation of smooth muscle cells (SMCs) at the site of lesion development. In the mouse model, the effectiveness of cyclooxygenase-2 (COX-2) inhibition for attenuating AAA progression is associated with maintenance of a differentiated SMC phenotype. However, the safety of COX-2 inhibitors is currently in question due to the increased ...


Non-Raft Ac2 Defines A Camp Signaling Compartment That Selectively Regulates Il-6 Expression In Airway Smooth Muscle Cells, Amy S. Bogard, Anna V. Birg, Rennolds S. Ostrom Jan 2014

Non-Raft Ac2 Defines A Camp Signaling Compartment That Selectively Regulates Il-6 Expression In Airway Smooth Muscle Cells, Amy S. Bogard, Anna V. Birg, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

Adenylyl cyclase (AC) isoforms differ in their tissue distribution, cellular localization, regulation, and protein interactions. Most cell types express multiple AC isoforms. We hypothesized that cAMP produced by different AC isoforms regulates unique cellular responses in human bronchial smooth muscle cells (BSMC). Overexpression of AC2, AC3, or AC6 had distinct effects on forskolin (Fsk)-induced expression of a number of known cAMP-responsive genes. These data show that different AC isoforms can differentially regulate gene expression. Most notable, overexpression and activation of AC2 enhanced interleukin 6 (IL-6) expression, but overexpression of AC3 or AC6 had no effect. IL-6 production by BSMC ...


Mutant Tdp-43 Deregulates Ampk Activation By Pp2a In Als Models, Nirma Perera, Rebecca Sheean, John Scott, Bruce Kemp, Malcolm Horne, Bradley Turner Jan 2014

Mutant Tdp-43 Deregulates Ampk Activation By Pp2a In Als Models, Nirma Perera, Rebecca Sheean, John Scott, Bruce Kemp, Malcolm Horne, Bradley Turner

Faculty of Health Sciences Publications

Bioenergetic abnormalities and metabolic dysfunction occur in amyotrophic lateral sclerosis (ALS) patients and genetic mouse models. However, whether metabolic dysfunction occurs early in ALS pathophysiology linked to different ALS genes remains unclear. Here, we investigated AMP-activated protein kinase (AMPK) activation, which is a key enzyme induced by energy depletion and metabolic stress, in neuronal cells and mouse models expressing mutant superoxide dismutase 1 (SOD1) or TAR DNA binding protein 43 (TDP-43) linked to ALS. AMPK phosphorylation was sharply increased in spinal cords of transgenic SOD1G93A mice at disease onset and accumulated in cytoplasmic granules in motor neurons, but not in ...