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Articles 1 - 30 of 3435

Full-Text Articles in Cell Biology

Directed Cell Migration In Multi-Cue Environments, Laura Lara Rodriguez, Ian C. Schneider Apr 2019

Directed Cell Migration In Multi-Cue Environments, Laura Lara Rodriguez, Ian C. Schneider

Ian C. Schneider

Cell migration plays a critical role in development, angiogenesis, immune response, wound healing and cancer metastasis. During these processes, cells are often directed to migrate towards targets by sensing aligned fibers or gradients in concentration, mechanical properties or electric field. Often times, cells must integrate migrational information from several of these different cues. While the cell migration behavior, signal transduction and cytoskeleton dynamics elicited by individual directional cues has been largely determined, responses to multiple directional cues are much less understood. However, initial work has pointed to several interesting behaviors in multi-cue environments, including competition and cooperation between cues to ...


A Cell Cycle Cue Triggers Cell Growth Resumption After Division, Afton R. Russell Apr 2019

A Cell Cycle Cue Triggers Cell Growth Resumption After Division, Afton R. Russell

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

The decoupling of the fundamental processes of cell division and growth is important for maintaining cell integrity. Through a chemical approach, we delayed the clock that controls when cells separate, uncoupling cell division and cell growth. This led to polarized cell growth before the cells completed separation. Using fluorescent markers to denote the cell’s stage in the cell cycle, we observed that only cells that were in mitosis exhibited this uncoupling. Previously it was thought that growth resumption occurred after completion of cell division, but this observation suggests that growth is triggered earlier, from a mitotic cue. This mitotic ...


Hexavalent Chromium: Elucidating Its Carcinogenic Mechanism, And Testing Potential Preventative Treatments, Ryan Himes, Timothy Mayotte Apr 2019

Hexavalent Chromium: Elucidating Its Carcinogenic Mechanism, And Testing Potential Preventative Treatments, Ryan Himes, Timothy Mayotte

Scholar Week 2016 - present

Cr(VI) (hexavalent chromium) has recently been found in the drinking water of over 250 million Americans. It is a powerful oxidizing agent, and is known to cause cancer, although the specific mechanism has yet to be elucidated. There is no known preventative treatment for Cr(VI) exposure, and the US EPA is currently determining what concentration of Cr(VI) in drinking water can be safely tolerated. This study sought to test the hypothesis that Cr(VI) cytotoxicity can be prevented by various antioxidants. We tested this hypothesis by exposing human embryonic kidney and human intestinal epithelial cells to Cr ...


Alpha Mangostin As A Chemoprotective Agent Via Activation Of The P53 Pathway For Breast Cancer, Vanessa Van Oost Apr 2019

Alpha Mangostin As A Chemoprotective Agent Via Activation Of The P53 Pathway For Breast Cancer, Vanessa Van Oost

Scholar Week 2016 - present

Breast carcinoma is the most frequently diagnosed cancer among women and causes over 400,000 deaths yearly worldwide. Current treatments such as chemotherapy are not selective for cancerous tissues but are destructive to normal tissues as well. This causes a range of side effects including pain, nausea, hair loss, weakness, and more. Inactivation of p53 is an almost universal mutation within human cancer cells. The ability to activate the p53 pathway which protects cells from tumor formation is lost in 50% of cancers. Due to the prevalence of this mutation, p53 is a uniquely valuable target for applied research. Alpha ...


A Screen For Genetic Modifiers Of Protein Phosphatase 1 Function In Drosophila Collective Cell Cohesion And Migration, Carmen F. Del Real, Yujun Chen, Marissa Komp, Jocelyn A. Mcdonald Apr 2019

A Screen For Genetic Modifiers Of Protein Phosphatase 1 Function In Drosophila Collective Cell Cohesion And Migration, Carmen F. Del Real, Yujun Chen, Marissa Komp, Jocelyn A. Mcdonald

Kansas State University Undergraduate Research Conference

Cells can migrate collectively in tightly or loosely-associated groups during tissue and organ formation, during embryonic development, in tumor metastases, and in wound healing. Drosophilaborder cellsserve as an excellent genetic model of collective cell migration inside a developing tissue. During ovarian development, 6-8 cells form the border cell cluster and migrate together as a cohesive group to reach the large oocyte. Previous experiments have shown that Nuclear inhibitor of Protein Serine Threonine Phosphatase 1 (NiPP1) causes border cells to separate into single cells, rather than stay in a group, and limits their ability to migrate. NiPP1 inhibits the ...


Using Arabidopsis Mesophyll Protoplasts To Study Unfolded Protein Response Signaling, Yan Bao, Diane C. Bassham Apr 2019

Using Arabidopsis Mesophyll Protoplasts To Study Unfolded Protein Response Signaling, Yan Bao, Diane C. Bassham

Diane Bassham

Various environmental stresses or artificial reagents can trigger unfolded protein accumulation in the endoplasmic reticulum (ER) due to the folding capacity of the ER being exceeded. This is termed ER stress, and triggers the unfolded protein response (UPR). Assays for activation of the UPR in plants include Tunicamycin (Tm)- or dithiothreitol (DTT)-mediated root growth inhibition, analysis of splicing of the UPR-responsive transcription factor bZIP60 (basic Leucine Zipper Domain 60), and upregulation of relevant UPR genes. We provide here a quick and robust method to detect UPR signaling in Arabidopsis thaliana protoplasts. This assay can also be applied to other ...


Snrk1 Activates Autophagy Via The Tor Signaling Pathway In Arabidopsis Thaliana, Junmarie Soto-Burgos, Diane C. Bassham Apr 2019

Snrk1 Activates Autophagy Via The Tor Signaling Pathway In Arabidopsis Thaliana, Junmarie Soto-Burgos, Diane C. Bassham

Diane Bassham

Autophagy is a degradation process in which cells break down and recycle their cytoplasmic contents when subjected to environmental stress or during cellular remodeling. The Arabidopsis thaliana SnRK1 complex is a protein kinase that senses changes in energy levels and triggers downstream responses to enable survival. Its mammalian ortholog, AMPK, and yeast ortholog, Snf-1, activate autophagy in response to low energy conditions. We therefore hypothesized that SnRK1 may play a role in the regulation of autophagy in response to nutrient or energy deficiency in Arabidopsis. To test this hypothesis, we determined the effect of overexpression or knockout of the SnRK1 ...


Tor-Dependent And -Independent Pathways Regulate Autophagy In Arabidopsis Thaliana, Yunting Pu, Xinjuan Luo, Diane C. Bassham Apr 2019

Tor-Dependent And -Independent Pathways Regulate Autophagy In Arabidopsis Thaliana, Yunting Pu, Xinjuan Luo, Diane C. Bassham

Diane Bassham

Autophagy is a critical process for recycling of cytoplasmic materials during environmental stress, senescence and cellular remodeling. It is upregulated under a wide range of abiotic stress conditions and is important for stress tolerance. Autophagy is repressed by the protein kinase target of rapamycin (TOR), which is activated in response to nutrients and in turn upregulates cell growth and translation and inhibits autophagy. Down-regulation of TOR in Arabidopsis thaliana leads to constitutive autophagy and to decreased growth, but the relationship to stress conditions is unclear. Here, we assess the extent to which TOR controls autophagy activation by abiotic stress. Overexpression ...


Tno1, A Tgn-Localized Snare-Interacting Protein, Modulates Root Skewing In Arabidopsis Thaliana, Rahul Roy, Diane C. Bassham Apr 2019

Tno1, A Tgn-Localized Snare-Interacting Protein, Modulates Root Skewing In Arabidopsis Thaliana, Rahul Roy, Diane C. Bassham

Diane Bassham

Background: The movement of plant roots within the soil is key to their ability to interact with the environment and maximize anchorage and nutrient acquisition. Directional growth of roots occurs by a combination of sensing external cues, hormonal signaling and cytoskeletal changes in the root cells. Roots growing on slanted, impenetrable growth medium display a characteristic waving and skewing, and mutants with deviations in these phenotypes assist in identifying genes required for root movement. Our study identifies a role for a trans-Golgi network-localized protein in root skewing.

Results: We found that Arabidopsis thaliana TNO1 (TGN-localized SYP41-interacting protein), a putative tethering ...


Cellular Dynamics: Cellular Systems In The Time Domain, Dan Szymanski, Diane Bassham, Teun Munnik, Wataru Sakamoto Apr 2019

Cellular Dynamics: Cellular Systems In The Time Domain, Dan Szymanski, Diane Bassham, Teun Munnik, Wataru Sakamoto

Diane Bassham

Plant cells are the fundamental building blocks of growth and development. For each cell type, the size, shape, and mechanical properties of the cell wall are customized for particular physiological functions (Szymanski and Cosgrove, 2009; Winship et al., 2011). The morphogenesis of highly polarized cell types such as trichoblasts and pollen tubes is internally programmed and occurs largely in the absence of a neighbor. Most cell types differentiate in the context of a tissue. Therefore, their growth and shape change can operate at larger spatial scales to influence tissue- and organ-level processes. Because plant cells grow symplastically and are mechanically ...


A Functional Unfolded Protein Response Is Required For Normal Vegetative Development, Yan Bao, Diane C. Bassham, Stephen H. Howell Apr 2019

A Functional Unfolded Protein Response Is Required For Normal Vegetative Development, Yan Bao, Diane C. Bassham, Stephen H. Howell

Diane Bassham

The unfolded protein response (UPR) is activated in plants in response to endoplasmic reticulum stress and plays an important role in mitigating stress damage. Multiple factors act in the UPR, including the membrane-associated transcription factor, BASIC LEUCINE ZIPPER 17 (bZIP17), and the membrane-associated RNA splicing factor, INOSITOL REQUIRING ENZYME1 (IRE1). We have analyzed an Arabidopsis (Arabidopsis thaliana) ire1a ire1b bzip17 triple mutant, with defects in stress signaling, and found that the mutant is also impaired in vegetative plant growth under conditions without externally applied stress. This raised the possibility that the UPR functions in plant development in the same manner ...


Autophagy In Crop Plants: What's New Beyond Arabidopsis?, Jie Tang, Diane C. Bassham Apr 2019

Autophagy In Crop Plants: What's New Beyond Arabidopsis?, Jie Tang, Diane C. Bassham

Diane Bassham

Autophagy is a major degradation and recycling pathway in plants. It functions to maintain cellular homeostasis and is induced by environmental cues and developmental stimuli. Over the past decade, the study of autophagy has expanded from model plants to crop species. Many features of the core machinery and physiological functions of autophagy are conserved among diverse organisms. However, several novel functions and regulators of autophagy have been characterized in individual plant species. In light of its critical role in development and stress responses, a better understanding of autophagy in crop plants may eventually lead to beneficial agricultural applications. Here, we ...


Recombinant Netrin-4 Does Not Signal Through The Netrin-1 Or Netrin-3 Pathway In Tetrahymena Thermophila, Nicholas Bradley, Heather G. Kuruvilla Apr 2019

Recombinant Netrin-4 Does Not Signal Through The Netrin-1 Or Netrin-3 Pathway In Tetrahymena Thermophila, Nicholas Bradley, Heather G. Kuruvilla

Heather G. Kuruvilla, Ph.D.

Netrin 4 protein and its homologs are found throughout the animal kingdom. Netrin-4 is known to have a protective role against vascular damage. Previous studies have shown that human netrin-1 has a role in angiogenesis. This information about human netrin-1 and netrin-4 led us to research the pathway of netrin-4 in Tetrahymena thermophila. Our previous studies of the netrin proteins show that netrin-1 and netrin-3 are both repellents in Tetrahymena thermophila. The data in this study show that netrin-4 is also a repellent of Tetrahymena thermophila. These data suggest that netrin-4 could signal through the same pathway as netrin-1 and ...


Selective Autophagy Of Bes1 Mediated By Dsk2 Balances Plant Growth And Survival, Trevor M. Nolan, Benjamin Brennan, Mengran Yang, Jiani Chen, Mingcai Zhang, Zhaohu Li, Xuelu Wang, Diane C. Bassham, Justin Walley, Yanhai Yin Apr 2019

Selective Autophagy Of Bes1 Mediated By Dsk2 Balances Plant Growth And Survival, Trevor M. Nolan, Benjamin Brennan, Mengran Yang, Jiani Chen, Mingcai Zhang, Zhaohu Li, Xuelu Wang, Diane C. Bassham, Justin Walley, Yanhai Yin

Diane Bassham

Plants encounter a variety of stresses and must fine-tune their growth and stress-response programs to best suit their environment. BES1 functions as a master regulator in the brassinosteroid (BR) pathway that promotes plant growth. Here, we show that BES1 interacts with the ubiquitin receptor protein DSK2 and is targeted to the autophagy pathway during stress via the interaction of DSK2 with ATG8, a ubiquitin-like protein directing autophagosome formation and cargo recruitment. Additionally, DSK2 is phosphorylated by the GSK3-like kinase BIN2, a negative regulator in the BR pathway. BIN2 phosphorylation of DSK2 flanking its ATG8 interacting motifs (AIMs) promotes DSK2-ATG8 interaction ...


Stochastic Optical Reconstruction Microscopy Imaging Of Microtubule Arrays In Intact Arabidopsis Thaliana Seedling, Bin Dong, Xiaochen Yang, Shaobin Zhu, Diane C. Bassham, Ning Fang Apr 2019

Stochastic Optical Reconstruction Microscopy Imaging Of Microtubule Arrays In Intact Arabidopsis Thaliana Seedling, Bin Dong, Xiaochen Yang, Shaobin Zhu, Diane C. Bassham, Ning Fang

Diane Bassham

Super-resolution fluorescence microscopy has generated tremendous success in revealing detailed subcellular structures in animal cells. However, its application to plant cell biology remains extremely limited due to numerous technical challenges, including the generally high fluorescence background of plant cells and the presence of the cell wall. In the current study, stochastic optical reconstruction microscopy (STORM) imaging of intact Arabidopsis thaliana seedling roots with a spatial resolution of 20–40 nm was demonstrated. Using the super-resolution images, the spatial organization of cortical microtubules in different parts of a whole Arabidopsis root tip was analyzed quantitatively, and the results show the dramatic ...


Recombinant Netrin-4 Does Not Signal Through The Netrin-1 Or Netrin-3 Pathway In Tetrahymena Thermophila, Nicholas Bradley, Heather G. Kuruvilla Apr 2019

Recombinant Netrin-4 Does Not Signal Through The Netrin-1 Or Netrin-3 Pathway In Tetrahymena Thermophila, Nicholas Bradley, Heather G. Kuruvilla

The Research and Scholarship Symposium

Netrin 4 protein and its homologs are found throughout the animal kingdom. Netrin-4 is known to have a protective role against vascular damage. Previous studies have shown that human netrin-1 has a role in angiogenesis. This information about human netrin-1 and netrin-4 led us to research the pathway of netrin-4 in Tetrahymena thermophila. Our previous studies of the netrin proteins show that netrin-1 and netrin-3 are both repellents in Tetrahymena thermophila. The data in this study show that netrin-4 is also a repellent of Tetrahymena thermophila. These data suggest that netrin-4 could signal through the same pathway as netrin-1 and ...


Tetrahymena Thermophila Lack A Homologue Of The Caenorhabditis Elegans Lin-4 Mirna, Bryce H. Childers, Sorrel Paris, Emma Wessels, Heather G. Kuruvilla Apr 2019

Tetrahymena Thermophila Lack A Homologue Of The Caenorhabditis Elegans Lin-4 Mirna, Bryce H. Childers, Sorrel Paris, Emma Wessels, Heather G. Kuruvilla

The Research and Scholarship Symposium

The netrin family of proteins was first discovered because of their role in axonal guidance during development. Netrin homologues are important developmental signals in organisms ranging from vertebrates to the nematode, Caenorhabditis elegans, and netrin-like proteins have even been found in the ciliated protozoan, Tetrahymena thermophila. Since the lin-4 miRNA regulates netrin signaling in C. elegans, we hypothesized that a lin-4 homologue might exists in Tetrahymena thermophila. In order to test this hypothesis, we purified total miRNA from T. thermophila, used this miRNA to make cDNA, then used RT-PCR to quantitate the amount of lin-4 specific cDNA we obtained. Our ...


A Functional Unfolded Protein Response Is Required For Normal Vegetative Development, Yan Bao, Diane C. Bassham, Stephen H. Howell Apr 2019

A Functional Unfolded Protein Response Is Required For Normal Vegetative Development, Yan Bao, Diane C. Bassham, Stephen H. Howell

Genetics, Development and Cell Biology Publications

The unfolded protein response (UPR) is activated in plants in response to endoplasmic reticulum stress and plays an important role in mitigating stress damage. Multiple factors act in the UPR, including the membrane-associated transcription factor, BASIC LEUCINE ZIPPER 17 (bZIP17), and the membrane-associated RNA splicing factor, INOSITOL REQUIRING ENZYME1 (IRE1). We have analyzed an Arabidopsis (Arabidopsis thaliana) ire1a ire1b bzip17 triple mutant, with defects in stress signaling, and found that the mutant is also impaired in vegetative plant growth under conditions without externally applied stress. This raised the possibility that the UPR functions in plant development in the same manner ...


X-Inactivation And Epigenetics, Serena Weston Apr 2019

X-Inactivation And Epigenetics, Serena Weston

Thinking Matters Symposium

To prevent abnormal development caused by expressing both X chromosomes, female mammals inactivate one of their X chromosomes using an epigenetic process called dosage compensation. This literature review examines how X chromosome inactivation (XCI) occurs during the formation and development of an embryo. This condensation of DNA is marked by histone tail modifications, DNA methylation, and the arrival of structural proteins resulting in extraordinarily stable heterochromatin. X-inactivation is regulated in cis by the X-inactivation center (Xic) that contains the Xist gene and its antisense gene, Tsix. On one X chromosome, Xist RNA is expressed and coats the center of the ...


Ultrafine Carbon Nanoparticles Activate Inflammasome Signaling And Cell Death In Murine Macrophages, Alexander Soloniuk, Hadley Lamascus, Jay Brewster, John Mann Mar 2019

Ultrafine Carbon Nanoparticles Activate Inflammasome Signaling And Cell Death In Murine Macrophages, Alexander Soloniuk, Hadley Lamascus, Jay Brewster, John Mann

Seaver College Research And Scholarly Achievement Symposium

Carbon black (CB) is the primary nanoparticulate component of air pollution from fossil fuel combustion. This work examines the cellular impact of ultrafine carbon (carbon black, CB) nanoparticles, that range in size down to 30 nm, upon murine macrophages. The size analysis of the carbon black nanoparticles was performed using atomic force microscopy (AFM) and transmission electron microscopy (TEM) techniques. RAW246.7 macrophage cells were exposed to CB doses ranging from 50 – 200 ug/ml in complete media. Analysis of cell survival over time revealed elevated rates of significant nuclear degradation and cell lifting after 48 hours of exposure, and ...


Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio Mar 2019

Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio

Arthur M. Mercurio

The function of vascular endothelial growth factor (VEGF) in cancer extends beyond angiogenesis and vascular permeability. Specifically, VEGF-mediated signaling occurs in tumor cells and this signaling contributes to key aspects of tumorigenesis including the self-renewal and survival of cancer stem cells (CSCs). In addition to VEGF receptor tyrosine kinases, the neuropilins (NRPs) are critical for mediating the effects of VEGF on CSCs, primarily because of their ability to impact the function of growth factor receptors and integrins. VEGF/NRP signaling can regulate the expression and function of key molecules that have been implicated in CSC function including Rho family guanosine ...


Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo Mar 2019

Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage- and pathogen-associated molecular patterns contribute to a self-perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a surface receptor that amplifies inflammation induced by toll-like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM-1 signaling contributes to proinflammatory pathway activation in ALD. Using an in vivo ALD model in mice, we tested the effects of ligand-independent TREM-1 inhibitory peptides that were formulated into human high-density lipoprotein (HDL)-mimicking complexes GF9-HDL and GA ...


Constitutive Interferon Signaling Maintains Critical Threshold Of Mlkl Expression To License Necroptosis, Joseph Sarhan, Beiyun C. Liu, Hayley I. Muendlein, Chi G. Weindel, Irina Smirnova, Amy Y. Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A. Fitzgerald, Alexander Poltorak Mar 2019

Constitutive Interferon Signaling Maintains Critical Threshold Of Mlkl Expression To License Necroptosis, Joseph Sarhan, Beiyun C. Liu, Hayley I. Muendlein, Chi G. Weindel, Irina Smirnova, Amy Y. Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A. Fitzgerald, Alexander Poltorak

Katherine A. Fitzgerald

Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein. We found that the pre-established IFN status of the cell, instead of LPS-induced IFN, is critical for the early initiation of necroptosis in macrophages. This pre-established IFN signature stems from cytosolic DNA sensing via cGAS ...


Molecular Basis For Strain Variation In The S. Cerevisiae Adhesion Flo11p, Li Li Ph.D., Subit Barua, Peter N. Lipke, Anne M. Dranginis Mar 2019

Molecular Basis For Strain Variation In The S. Cerevisiae Adhesion Flo11p, Li Li Ph.D., Subit Barua, Peter N. Lipke, Anne M. Dranginis

Li Li

FLO11 encodes a yeast cell wall flocculin that mediates a variety of adhesive phenotypes in Saccharomyces cerevisiae. Flo11p is implicated in many developmental processes, including flocculation, formation of pseudohyphae, agar invasion, and formation of microbial mats and biofilms. However, Flo11p mediates different processes in different yeast strains. To investigate the mechanisms by which FLO11 determines these differences in colony morphology, flocculation, and invasion, we studied gene structure, function, and expression levels. Nonflocculent Saccharomyces cerevisiae Σ1278b cells exhibited significantly higher FLO11mRNA expression, especially in the stationary phase, than highly flocculent S. cerevisiae var. diastaticus. The two strains varied in cell ...


Expression And Characterization Of The Flocculin Flo11/Muc1, A Yeast Mannoprotein With Homotypic Properties Of Adhesion, Li Li Ph.D., Lois M. Douglas, Yang Yang, A M. Dranginis Mar 2019

Expression And Characterization Of The Flocculin Flo11/Muc1, A Yeast Mannoprotein With Homotypic Properties Of Adhesion, Li Li Ph.D., Lois M. Douglas, Yang Yang, A M. Dranginis

Li Li

The Flo11/Muc1 flocculin has diverse phenotypic effects. Saccharomyces cerevisiae cells of strain background Σ1278b require Flo11p to form pseudohyphae, invade agar, adhere to plastic, and develop biofilms, but they do not flocculate. We show that S. cerevisiae var. diastaticusstrains, on the other hand, exhibit Flo11-dependent flocculation and biofilm formation but do not invade agar or form pseudohyphae. In order to study the nature of the Flo11p proteins produced by these two types of strains, we examined secreted Flo11p, encoded by a plasmid-borne gene, in which the glycosylphosphatidylinositol anchor sequences had been replaced by a histidine tag. A protein ...


Endosome To Golgi Retrieval Of The Vacuolar Protein Sorting Receptor, Vps10p, Requires The Function Of The Vps29, Vps30, And Vps35 Gene Products, Matthew N. J. Seaman, Eric G. Marcusson, Joan Lin-Cereghino, Scott D. Emr Mar 2019

Endosome To Golgi Retrieval Of The Vacuolar Protein Sorting Receptor, Vps10p, Requires The Function Of The Vps29, Vps30, And Vps35 Gene Products, Matthew N. J. Seaman, Eric G. Marcusson, Joan Lin-Cereghino, Scott D. Emr

Joan Lin-Cereghino

Mutations in the S. cerevisiae VPS29 and VPS30 genes lead to a selective protein sorting defect in which the vacuolar protein carboxypeptidase Y (CPY) is missorted and secreted from the cell, while other soluble vacuolar hydrolases like proteinase A (PrA) are delivered to the vacuole. This phenotype is similar to that seen in cells with mutations in the previously characterized VPS10 and VPS35 genes. Vps10p is a late Golgi transmembrane protein that acts as the sorting receptor for soluble vacuolar hydrolases like CPY and PrA, while Vps35p is a peripheral membrane protein which cofractionates with membranes enriched in Vps10p. The ...


Receptor Interacting Protein Kinase 3 (Rip3) Regulates Ipscs Generation Through Modulating Cell Cycle Progression Genes, Ahmad Al-Moujahed, Bo Tian, Nikolaos E. Efstathiou, Eleni K. Konstantinou, Mien Hoang, Haijiang Lin, Joan W. Miller, Demetrios G. Vavvas Mar 2019

Receptor Interacting Protein Kinase 3 (Rip3) Regulates Ipscs Generation Through Modulating Cell Cycle Progression Genes, Ahmad Al-Moujahed, Bo Tian, Nikolaos E. Efstathiou, Eleni K. Konstantinou, Mien Hoang, Haijiang Lin, Joan W. Miller, Demetrios G. Vavvas

Open Access Articles

The molecular mechanisms involved in induced pluripotent stem cells (iPSCs) generation are poorly understood. The cell death machinery of apoptosis-inducing caspases have been shown to facilitate the process of iPSCs reprogramming. However, the effect of other cell death processes, such as programmed necrosis (necroptosis), on iPSCs induction has not been studied. In this study, we investigated the role of receptor-interacting protein kinase 3 (RIP3), an essential regulator of necroptosis, in reprogramming mouse embryonic fibroblast cells (MEFs) into iPSCs. RIP3 was found to be upregulated in iPSCs compared to MEFs. Deletion of RIP3 dramatically suppressed the reprogramming of iPSCs (~82%). RNA-seq ...


Investigating The Role Of Free Radicals In Huntington's Disease Using Drosophila Melanogaster, Jennifer Libov Mar 2019

Investigating The Role Of Free Radicals In Huntington's Disease Using Drosophila Melanogaster, Jennifer Libov

Honors Theses, University of Nebraska-Lincoln

During normal cell metabolism, reactive oxygen species (ROS) are produced as a byproduct of oxidative phosphorylation. ROS are utilized in the cell as a signaling molecule and can be maintained at healthy levels by cellular antioxidants. However, when the cell experiences oxidative stress due to environmental or genetic conditions, levels of ROS can exceed healthy levels and inhibit necessary life functions by damaging biomolecules and cellular structures. This loss of function can lead to physiological decline and neurodegeneration, such as in diseases like Alzheimer’s, amyotrophic lateral sclerosis (ALS), and, potentially, Huntington’s disease. The following experiments use the model ...


Viral Infection Or Ifn-Alpha Alters Mitotic Spindle Orientation By Modulating Pericentrin Levels, William M. Mcdougall, Jill Perreira, Hui-Fang Hung, Anastassiia Vertii, E. Xiaofei, Wendy Zimmerman, Timothy F. Kowalik, Stephen J. Doxsey, Abraham L. Brass Feb 2019

Viral Infection Or Ifn-Alpha Alters Mitotic Spindle Orientation By Modulating Pericentrin Levels, William M. Mcdougall, Jill Perreira, Hui-Fang Hung, Anastassiia Vertii, E. Xiaofei, Wendy Zimmerman, Timothy F. Kowalik, Stephen J. Doxsey, Abraham L. Brass

Open Access Articles

Congenital microcephaly occurs in utero during Zika virus (ZIKV) infection. The single-gene disorder, Majewski osteodysplastic primordial dwarfism type II (MOPDII), also leads to microcephaly and is concomitant with a decrease in the centrosomal protein, pericentrin (PCNT). This protein is a known contributor of mitotic spindle misorientation and ultimately, microcephaly. Similar to MOPDII, either viral infection or interferon (IFN)-alpha exposure reduced PCNT levels at the mitotic spindle poles. We unexpectedly found that infection of cells with any one of a diverse set of viruses, such as ZIKV, dengue virus, cytomegalovirus, influenza A virus, or hepatitis B virus, or treatment of ...


Huntingtin Associates With The Actin Cytoskeleton And Alpha-Actinin Isoforms To Influence Stimulus Dependent Morphology Changes, Adelaide Tousley, Maria Iuliano, Elizabeth Weisman, Ellen Sapp, Heather Richardson, Petr Vodicka, Jonathan Alexander, Neil Aronin, Marian Difiglia, Kimberly B. Kegel-Gleason Feb 2019

Huntingtin Associates With The Actin Cytoskeleton And Alpha-Actinin Isoforms To Influence Stimulus Dependent Morphology Changes, Adelaide Tousley, Maria Iuliano, Elizabeth Weisman, Ellen Sapp, Heather Richardson, Petr Vodicka, Jonathan Alexander, Neil Aronin, Marian Difiglia, Kimberly B. Kegel-Gleason

Open Access Articles

One response of cells to growth factor stimulus involves changes in morphology driven by the actin cytoskeleton and actin associated proteins which regulate functions such as cell adhesion, motility and in neurons, synaptic plasticity. Previous studies suggest that Huntingtin may be involved in regulating morphology however, there has been limited evidence linking endogenous Huntingtin localization or function with cytoplasmic actin in cells. We found that depletion of Huntingtin in human fibroblasts reduced adhesion and altered morphology and these phenotypes were made worse with growth factor stimulation, whereas the presence of the Huntington's Disease mutation inhibited growth factor induced changes ...