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Full-Text Articles in Cell Biology

Role Of Jip1-Jnk Signaling In Beta-Cell Function And Autophagy, Seda Barutcu Jan 2018

Role Of Jip1-Jnk Signaling In Beta-Cell Function And Autophagy, Seda Barutcu

GSBS Dissertations and Theses

Proper functioning of endocrine cells is crucial for organismal homeostasis. The underlying mechanisms that fine-tune the amount, and the timing of hormone secretion are not clear. JIP1 / MAPK8IP1 (JNK interacting protein 1) is a scaffold protein that mediates cellular stress response, and is highly expressed in endocrine cells, including insulin secreting b-cells in pancreas islets. However, the role of JIP1 in b-cells is unclear. This study demonstrates that b-cell specific Jip1 ablation results in decreased glucose-induced insulin secretion, without a change in Insulin1 and Insulin2 gene expression. Inhibition of both JIP1-kinesin interaction, and JIP1-JNK interaction by genetic mutations also resulted ...


Intergenerational Effects Of Nicotine In An Animal Model Of Paternal Nicotine Exposure, Markus Parzival Vallaster Aug 2017

Intergenerational Effects Of Nicotine In An Animal Model Of Paternal Nicotine Exposure, Markus Parzival Vallaster

GSBS Dissertations and Theses

Environmental conditions imposed onto organisms during certain phases of their life cycles such as embryogenesis or puberty can not only impact the organisms’ own health, but also affect subsequent generations. The underlying mechanisms causing intergenerational phenotypes are not encoded in the genome, but the result of reversible epigenetic modifications. This work investigates in a mouse model the impact of paternal nicotine exposure on the next generation regarding addictive behavior modulation, metabolic changes, and molecular mechanisms. It provides evidence that male offspring from nicotine-exposed fathers (NIC offspring) is more resistant to lethal doses of nicotine. This phenotype is gender-specific and depends ...


Complement-Related Regulates Autophagy In Neighboring Cells, Lin Lin Jun 2017

Complement-Related Regulates Autophagy In Neighboring Cells, Lin Lin

GSBS Dissertations and Theses

Autophagy is a conserved process that cells use to degrade their own cytoplasmic components by delivery to lysosomes. Autophagy ensures intracellular quality control and is associated with diseases such as cancer and immune disorders. The process of autophagy is controlled by core autophagy (Atg) genes that are conserved from yeast to mammal. Most Atg proteins and their regulators were identified through pioneering studies of the single cell yeast Saccharomyces cerevisiae, and little is known about factors that systematically coordinate autophagy within the tissues of multicellular animals. The goal of this thesis is to identify new autophagy regulators and provide a ...


Role Of Energy Metabolism In The Thermogenic Gene Program, Minwoo Nam Jan 2017

Role Of Energy Metabolism In The Thermogenic Gene Program, Minwoo Nam

GSBS Dissertations and Theses

In murine and human brown adipose tissue (BAT), mitochondria are powerful generators of heat. Emerging evidence has suggested that the actions of mitochondria extend beyond this conventional biochemical role. In mouse BAT and cultured brown adipocytes, impaired mitochondrial respiratory capacity is accompanied by attenuated expression of Ucp1, a key thermogenic gene, implying a mitochondrial retrograde signaling. However, few have investigated this association in the context of mitochondria-nucleus communication.

Using mice with adipose-specific ablation of LRPPRC, a regulator of respiratory capacity, we show that respiration-dependent retrograde signaling from mitochondria to nucleus contributes to transcriptional and metabolic reprogramming of BAT. Impaired respiratory ...


Roles Of The Mother Centriole Appendage Protein Cenexin In Microtubule Organization During Cell Migration And Cell Division: A Dissertation, Hui-Fang Hung Aug 2016

Roles Of The Mother Centriole Appendage Protein Cenexin In Microtubule Organization During Cell Migration And Cell Division: A Dissertation, Hui-Fang Hung

GSBS Dissertations and Theses

Epithelial cells are necessary building blocks of the organs they line. Their apicalbasolateral polarity, characterized by an asymmetric distribution of cell components along their apical-basal axis, is a requirement for normal organ function. Although the centrosome, also known as the microtubule organizing center, is important in establishing cell polarity the mechanisms through which it achieves this remain unclear. It has been suggested that the centrosome influences cell polarity through microtubule cytoskeleton organization and endosome trafficking. In the first chapter of this thesis, I summarize the current understanding of the mechanisms regulating cell polarity and review evidence for the role of ...


A Role For Tnmd In Adipocyte Differentiation And Adipose Tissue Function: A Dissertation, Ozlem Senol-Cosar Jun 2016

A Role For Tnmd In Adipocyte Differentiation And Adipose Tissue Function: A Dissertation, Ozlem Senol-Cosar

GSBS Dissertations and Theses

Adipose tissue is one of the most dynamic tissues in the body and is vital for metabolic homeostasis. In the case of excess nutrient uptake, adipose tissue expands to store excess energy in the form of lipids, and in the case of reduced nutrient intake, adipose tissue can shrink and release this energy. Adipocytes are most functional when the balance between these two processes is intact. To understand the molecular mechanisms that drive insulin resistance or conversely preserve the metabolically healthy state in obese individuals, our laboratory performed a screen for differentially regulated adipocyte genes in insulin resistant versus insulin ...


Mechanisms Regulating Early Mesendodermal Differentiation Of Human Embryonic Stem Cells: A Dissertation, Jennifer J. Vanoudenhove Jun 2016

Mechanisms Regulating Early Mesendodermal Differentiation Of Human Embryonic Stem Cells: A Dissertation, Jennifer J. Vanoudenhove

GSBS Dissertations and Theses

Key regulatory events take place at very early stages of human embryonic stem cell (hESC) differentiation to accommodate their ability to differentiate into different lineages; this work examines two separate regulatory events.

To investigate precise mechanisms that link alterations in the cell cycle and early differentiation, we examined the initial stages of mesendodermal lineage commitment and observed a cell cycle pause that occurred concurrently with an increase in genes that regulate the G2/M transition, including WEE1. Inhibition of WEE1 prevented the G2 pause. Directed differentiation of hESCs revealed that cells paused during commitment to the endo- and mesodermal, but ...


Xist And Cot-1 Repeat Rnas Are Integral Components Of A Complex Nuclear Scaffold Required To Maintain Saf-A And Modify Chromosome Architecture: A Dissertation, Heather J. Kolpa Apr 2016

Xist And Cot-1 Repeat Rnas Are Integral Components Of A Complex Nuclear Scaffold Required To Maintain Saf-A And Modify Chromosome Architecture: A Dissertation, Heather J. Kolpa

GSBS Dissertations and Theses

XIST RNA established the precedent for a noncoding RNA that stably associates with and regulates chromatin, however it remains poorly understood how such RNAs structurally associate with the interphase chromosome territory. I demonstrate that transgenic XIST RNA localizes in cis to an autosome as it does to the inactive X chromosome, hence the RNA recognizes a structure common to all chromosomes. I reassess the prevalent thinking in the field that a single protein, Scaffold Attachment Factor-A (SAF-A/hnRNP U), provides a single molecule bridge required to directly tether the RNA to DNA. In an extensive series of experiments in multiple ...


A Role For The Lipid Droplet Protein Hig2 In Promoting Lipid Deposition In Liver And Adipose Tissue: A Dissertation, Marina T. Distefano Mar 2016

A Role For The Lipid Droplet Protein Hig2 In Promoting Lipid Deposition In Liver And Adipose Tissue: A Dissertation, Marina T. Distefano

GSBS Dissertations and Theses

Chronic exposure of humans or rodents to high calorie diets leads to hypertriglyceridemia and ectopic lipid deposition throughout the body, resulting in metabolic disease. Cellular lipids are stored in organelles termed lipid droplets (LDs) that are regulated by tissue-specific LD proteins. These proteins are critical for lipid homeostasis, as humans with LD protein mutations manifest metabolic dysfunction. Identification of novel components of the LD machinery could shed light on human disease mechanisms and suggest potential therapeutics for Type 2 Diabetes.

Microarray analyses pinpointed the largely unstudied Hypoxia-Inducible Gene 2 (Hig2) as a gene that was highly expressed in obese human ...


Systematic Dissection Of Roles For Chromatin Regulators In Dynamics Of Transcriptional Response To Stress In Yeast: A Dissertation, Hsiuyi V. Chen Dec 2015

Systematic Dissection Of Roles For Chromatin Regulators In Dynamics Of Transcriptional Response To Stress In Yeast: A Dissertation, Hsiuyi V. Chen

GSBS Dissertations and Theses

The following work demonstrates that chromatin regulators play far more pronounced roles in dynamic gene expression than they do in steady-state. Histone modifications have been associated with transcription activity. However, previous analyses of gene expression in mutants affecting histone modifications show limited alteration. I systematically dissected the effects of 83 histone mutants and 119 gene deletion mutants on gene induction/repression in response to diamide stress in yeast. Importantly, I observed far more changes in gene induction/repression than changes in steady-state gene expression. The extensive dynamic gene expression profile of histone mutants and gene deletion mutants also allowed me ...


Roles Of Protein Arginine Methyltransferase 7 And Jumonji Domain-Containing Protein 6 In Adipocyte Differentiation: A Dissertation, Yu-Jie Hu Oct 2015

Roles Of Protein Arginine Methyltransferase 7 And Jumonji Domain-Containing Protein 6 In Adipocyte Differentiation: A Dissertation, Yu-Jie Hu

GSBS Dissertations and Theses

Regulation of gene expression comprises a wide range of mechanisms that control the abundance of gene products in response to environmental and developmental changes. These biological processes can be modulated by posttranslational modifications including arginine methylation. Among the enzymes that catalyze the methylation, protein arginine methyltransferase 7 (PRMT7) is known to modify histones to repress gene expression. Jumonji domain-containing protein 6 (JMJD6) is a putative arginine demethylase that potentially antagonize PRMT7. However, the biological significance of these enzymes is not well understood. This thesis summarizes the investigation of both PRMT7 and JMJD6 in cell culture models for adipocyte differentiation. The ...


Exploring The Role Of Fus Mutants From Stress Granule Incorporation To Nucleopathy In Amyotrophic Lateral Sclerosis: A Dissertation, Hae Kyung Ko Sep 2015

Exploring The Role Of Fus Mutants From Stress Granule Incorporation To Nucleopathy In Amyotrophic Lateral Sclerosis: A Dissertation, Hae Kyung Ko

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by preferential motor neuron death in the brain and spinal cord. The rapid disease progression results in death due to respiratory failure, typically within 3-5 years after disease onset. While ~90% of cases occur sporadically, remaining 10% of ALS cases show familial inheritance, and the number of genes linked to ALS has increased dramatically over the past decade.

FUS/TLS (Fused in Sarcoma/ Translocated to liposarcoma) is a nucleic acid binding protein that may regulate several cellular functions, including RNA splicing, transcription, DNA damage repair and microRNA biogenesis. More than ...


Investigating The Effects Of Mutant Fus On Stress Response In Amyotrophic Lateral Sclerosis: A Thesis, Laura J. Kaushansky Aug 2015

Investigating The Effects Of Mutant Fus On Stress Response In Amyotrophic Lateral Sclerosis: A Thesis, Laura J. Kaushansky

GSBS Dissertations and Theses

During stress, eukaryotes regulate protein synthesis in part through formation of cytoplasmic, non-membrane-bound complexes called stress granules (SGs). SGs transiently store signaling proteins and stalled translational complexes in response to stress stimuli (e.g. oxidative insult, DNA damage, temperature shifts and ER dysfunction). The functional outcome of SGs is proper translational regulation and signaling, allowing cells to overcome stress.

The fatal motor neuron disease Amyotrophic Lateral Sclerosis (ALS) develops in an age-related manner and is marked by progressive neuronal death, with cytoplasmic protein aggregation, excitotoxicity and increased oxidative stress as major hallmarks. Fused in Sarcoma/Translocated in Liposarcoma (FUS) is ...


Jun Kinases In Hematopoiesis, And Vascular Development And Function: A Dissertation, Kasmir Ramo Jul 2015

Jun Kinases In Hematopoiesis, And Vascular Development And Function: A Dissertation, Kasmir Ramo

GSBS Dissertations and Theses

Arterial occlusive diseases are major causes of morbidity and mortality in industrialized countries and represent a huge economic burden. The extent of the native collateral circulation is an important determinant of blood perfusion restoration and therefore the severity of tissue damage and functional impairment that ensues following arterial occlusion. Understanding the mechanisms responsible for collateral artery development may provide avenues for therapeutic intervention. Here, we identify a critical requirement for mixed lineage kinase (MLK) – cJun-NH2-terminal kinase (JNK) signaling in vascular morphogenesis and native collateral artery development. We demonstrate that Mlk2-/-Mlk3-/- mice or mice with compound JNK-deficiency in the vascular ...


Cell Size Control In The Fission Yeast Schizosaccharomyces Pombe: A Dissertation, Daniel L. Keifenheim Jun 2015

Cell Size Control In The Fission Yeast Schizosaccharomyces Pombe: A Dissertation, Daniel L. Keifenheim

GSBS Dissertations and Theses

The coordination between cell growth and division is a highly regulated process that is intimately linked to the cell cycle. Efforts to identify an independent mechanism that measures cell size have been unsuccessful. Instead, we propose that size control is an intrinsic function of the basic cell cycle machinery.

My work shows that in the fission yeast Schizosaccharomyces pombe Cdc25 accumulates in a size dependent manner. This accumulation of Cdc25 occurs over a large range of cell sizes. Additionally, experiments with short pulses of cycloheximide have shown that Cdc25 is an inherently unstable protein that quickly returns to a size ...


Cathosis: Cathepsins In Particle-Induced Inflammatory Cell Death: A Dissertation, Gregory M. Orlowski May 2015

Cathosis: Cathepsins In Particle-Induced Inflammatory Cell Death: A Dissertation, Gregory M. Orlowski

GSBS Dissertations and Theses

Sterile particles underlie the pathogenesis of numerous inflammatory diseases. These diseases can often become chronic and debilitating. Moreover, they are common, and include silicosis (silica), asbestosis (asbestos), gout (monosodium urate), atherosclerosis (cholesterol crystals), and Alzeihmer’s disease (amyloid Aβ). Central to the pathology of these diseases is a repeating cycle of particle-induced cell death and inflammation. Macrophages are the key cellular mediators thought to drive this process, as they are especially sensitive to particle-induced cell death and they are also the dominant producers of the cytokine responsible for much of this inflammation, IL-1β. In response to cytokines or microbial cues ...


Role And Regulation Of Autophagy During Developmental Cell Death In Drosophila Melanogaster: A Dissertation, Kirsten M. Tracy Apr 2015

Role And Regulation Of Autophagy During Developmental Cell Death In Drosophila Melanogaster: A Dissertation, Kirsten M. Tracy

GSBS Dissertations and Theses

Autophagy is a conserved catabolic process that traffics cellular components to the lysosome for degradation. Autophagy is required for cell survival during nutrient restriction, but it has also been implicated in programmed cell death. It is associated with several diseases, including cancer. Cancer is a disease characterized by aberrant cell growth and proliferation. To support this growth, the tumor cell often deregulates several metabolic processes, including autophagy. Interestingly, autophagy plays paradoxical roles in tumorigenesis. It has been shown to be both tumor suppressive through cell death mechanisms and tumor promoting through its cytoprotective properties. However, the mechanisms regulating the balance ...


A Tale Of Two Projects: Basis For Centrosome Amplification After Dna Damage And Practical Assessment Of Photodamage In Live-Cell Imaging: A Dissertation, Stephen Douthwright Apr 2015

A Tale Of Two Projects: Basis For Centrosome Amplification After Dna Damage And Practical Assessment Of Photodamage In Live-Cell Imaging: A Dissertation, Stephen Douthwright

GSBS Dissertations and Theses

This thesis comprises two separate studies that focus on the consequences of cellular damage. The first investigates the effects of DNA damage on centriole behavior and the second characterizes phototoxicity during live-cell imaging.

Cancer treatments such as ionizing radiation and/or chemotherapeutic DNA damaging agents are intended to kill tumor cells, but they also damage normal proliferating cells. Although centrosome amplification after DNA damage is a well-established phenomenon for transformed cells, it is not fully understood in untransformed cells. The presence of extra centrosomes in normal cell populations raises the chances of genomic instability, thus posing additional threats to patients ...


Microrna Regulation Of Autophagy During Programmed Cell Death: A Dissertation, Charles J. Nelson Mar 2015

Microrna Regulation Of Autophagy During Programmed Cell Death: A Dissertation, Charles J. Nelson

GSBS Dissertations and Theses

Autophagy delivers cytoplasmic material to the lysosome for degradation, and has been implicated in many cellular processes, including stress, infection, survival, and death. Although the regulation and role that autophagy plays in stress, infection, and survival is apparent, its involvement during cell death remains relatively unclear. In this thesis I summarize what is known about the roles autophagy can play in cell death, and the differences between the utilization of autophagy during nutrient deprivation and cell death. Utilizing Drosophila melanogaster as a model system, the roles autophagy plays in both of these contexts can be studied. The goal of this ...


Function And Regulation Of The Α6 Integrins In Mammary Epithelial Biology And Breast Cancer: A Dissertation, Cheng Chang Feb 2015

Function And Regulation Of The Α6 Integrins In Mammary Epithelial Biology And Breast Cancer: A Dissertation, Cheng Chang

GSBS Dissertations and Theses

Integrins have the ability to impact major aspects of epithelial biology including adhesion, migration, invasion, signaling and differentiation, as well as the formation and progression of cancer (Hynes 2002; Srichai and Zent 2010; Anderson et al. 2014). This thesis focuses on how integrins are regulated and function in the context of mammary epithelial biology and breast cancer with a specific focus on the α6 integrin heterodimers (α6β1 and α6β4). These integrins function primarily as receptors for the laminin family of extracellular matrix (ECM) proteins and they have been implicated in mammary gland biology and breast cancer (Friedrichs et al. 1995 ...


Calcium Dependent Regulatory Mechanism In Wolfram Syndrome: A Dissertation, Simin Lu Feb 2015

Calcium Dependent Regulatory Mechanism In Wolfram Syndrome: A Dissertation, Simin Lu

GSBS Dissertations and Theses

Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration. Two causative genes have been identified so far, WFS1 and WFS2, both encoding endoplasmic reticulum (ER) localized transmembrane proteins. Since WFS1 is involved in the ER stress pathway, Wolfram syndrome is considered an ER disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome, the molecular mechanism linking ER to the death of β cells and neurons has not been elucidated.

The endoplasmic reticulum (ER) is an organelle that forms a network of enclosed sacs and tubes that connect the nuclear membrane and other organelles including Golgi and ...


Higher-Order Unfolding Of Peri/Centric Satellite Heterochromatin Is An Early And Consistent Event In Cell Senescence: A Dissertation, Eric C. Swanson Dec 2014

Higher-Order Unfolding Of Peri/Centric Satellite Heterochromatin Is An Early And Consistent Event In Cell Senescence: A Dissertation, Eric C. Swanson

GSBS Dissertations and Theses

Cellular senescence is thought to play an essential role in many biological functions including tumor suppression and organismal aging. Senescent cells, which are permanently removed from the cell cycle, can be found both in vivo in many different tissue types and in vitro within cultures of non-immortalized cells. Despite their inability to proliferate, these cells persist and remain metabolically active for indefinite periods of time. This physiologic process occurs in response to a variety of cellular insults including oxidative stress, shortened telomeres, constitutive oncogene expression, and DNA damage, and can be initiated by upregulation of one of the two known ...


Small Rnas And Argonautes Provide A Paternal Epigenetic Memory Of Germline Gene Expression To Promote Thermotolerant Male Fertility: A Dissertation, Colin C. Conine Sep 2014

Small Rnas And Argonautes Provide A Paternal Epigenetic Memory Of Germline Gene Expression To Promote Thermotolerant Male Fertility: A Dissertation, Colin C. Conine

GSBS Dissertations and Theses

During each life cycle, gametes must preserve and pass on both genetic and epigenetic information, making the germline both immortal and totipotent. In the male germline the dramatic morphological transformation of a germ cell through meiosis, into a sperm competent for fertilization, while retaining this information is an incredible example of cellular differentiation. This process of spermatogenesis is inherently thermosensitive in numerous metazoa ranging from worms to man. Here, I describe the role of two redundant AGO-class paralogs, ALG-3/4, and their small RNA cofactors, in promoting thermotolerant male fertility in Caenorhabditis elegans. alg-3/4 double mutants exhibit temperature dependent ...


Pos-1 Regulation Of Endo-Mesoderm Identity In C. Elegans: A Dissertation, Ahmed M. Elewa Apr 2014

Pos-1 Regulation Of Endo-Mesoderm Identity In C. Elegans: A Dissertation, Ahmed M. Elewa

GSBS Dissertations and Theses

How do embryos develop with such poise from a single zygote to multiple cells with different identities, and yet survive? At the four-cell stage of the C. elegans embryo, only the blastomere EMS adopts the endo-mesoderm identity. This fate requires SKN-1, the master regulator of endoderm and mesoderm differentiation. However, in the absence of the RNA binding protein POS-1, EMS fails to fulfill its fate despite the presence of SKN-1. pos-1(-) embryos die gutless. Conversely, the RNA binding protein MEX-5 prevents ectoderm blastomeres from adopting the endo-mesoderm identity by repressing SKN-1. mex-5(-) embryos die with excess muscle at the expense ...


A Novel Autophagy Regulatory Mechanism That Functions During Programmed Cell Death: A Dissertation, Tsun-Kai Chang Sep 2013

A Novel Autophagy Regulatory Mechanism That Functions During Programmed Cell Death: A Dissertation, Tsun-Kai Chang

GSBS Dissertations and Theses

Autophagy is a cellular process that delivers cytoplasmic materials for degradation by the lysosomes. Autophagy-related (Atg) genes were identified in yeast genetic screens for vehicle formation under stress conditions, and Atg genes are conserved from yeast to human. When cells or animals are under stress, autophagy is induced and Atg8 (LC3 in mammal) is activated by E1 activating enzyme Atg7. Atg8-containing membranes form and surround cargos, close and mature to become the autophagosomes. Autophagosomes fuse with lysosomes, and cargos are degraded by lysosomal enzymes to sustain cell viability. Therefore, autophagy is most frequently considered to function in cell survival. Whether ...


Hiv-1 And The Nucleolus: A Role For Nucleophosmin/Npm1 In Viral Replication: A Dissertation, Tracy E. Schmidt Aug 2013

Hiv-1 And The Nucleolus: A Role For Nucleophosmin/Npm1 In Viral Replication: A Dissertation, Tracy E. Schmidt

GSBS Dissertations and Theses

The nucleolus is a plurifunctional organelle with dynamic protein exchange involved in diverse aspects of cell biology. Additionally, the nucleolus has been shown to have a role in the replication of numerous viruses, which includes HIV-1. Several groups have reported HIV-1 vRNA localization within the nucleolus. Moreover, it has been demonstrated the HIV-1 Rev protein localizes to the nucleolus and interacts with nucleolar proteins, including NPM1. Despite evidence for a nucleolar involvement during replication, a functional link has not been demonstrated. I investigated whether introncontaining vRNAs have a Rev-mediated nucleolar localization step prior to export. Furthermore, I examined whether NPM1 ...


Morphogenetic Requirements For Embryo Patterning And The Generation Of Stem Cell-Derived Mice: A Dissertation, Yeonsoo Yoon Jul 2013

Morphogenetic Requirements For Embryo Patterning And The Generation Of Stem Cell-Derived Mice: A Dissertation, Yeonsoo Yoon

GSBS Dissertations and Theses

Cell proliferation and differentiation are tightly regulated processes required for the proper development of multi-cellular organisms. To understand the effects of cell proliferation on embryo patterning in mice, we inactivated Aurora A, a gene essential for completion of the cell cycle. We discovered that inhibiting cell proliferation leads to different outcomes depending on the tissue affected. If the epiblast, the embryonic component, is compromised, it leads to gastrulation failure. However, when Aurora A is inactivated in extra-embryonic tissues, mutant embryos fail to properly establish the anteroposterior axis. Ablation of Aurora A in the epiblast eventually leads to abnormal embryos composed ...


A Role For Intraflagellar Transport Proteins In Mitosis: A Dissertation, Alison R. Bright Jun 2013

A Role For Intraflagellar Transport Proteins In Mitosis: A Dissertation, Alison R. Bright

GSBS Dissertations and Theses

Disruption of cilia proteins results in a range of disorders called ciliopathies. However, the mechanism by which cilia dysfunction contributes to disease is not well understood. Intraflagellar transport (IFT) proteins are required for ciliogenesis. They carry ciliary cargo along the microtubule axoneme while riding microtubule motors. Interestingly, IFT proteins localize to spindle poles in non-ciliated, mitotic cells, suggesting a mitotic function for IFT proteins. Based on their role in cilia, we hypothesized that IFT proteins regulate microtubule-based transport during mitotic spindle assembly. Biochemical investigation revealed that in mitotic cells IFT88, IFT57, IFT52, and IFT20 interact with dynein1, a microtubule motor ...


Investigation Of Multiple Concerted Mechanisms Underlying Stimulus-Induced G1 Arrest In Yeast: A Dissertation, Patricia A. Pope Jun 2013

Investigation Of Multiple Concerted Mechanisms Underlying Stimulus-Induced G1 Arrest In Yeast: A Dissertation, Patricia A. Pope

GSBS Dissertations and Theses

Progression through the cell cycle is tightly controlled, and the decision whether or not to enter a new cell cycle can be influenced by both internal and external cues. For budding yeast one such external cue is pheromone treatment, which can induce G1 arrest. Two distinct mechanisms are known to be involved in this arrest, one dependent on the arrest protein Far1 and one independent of Far1, but the exact mechanisms have remained enigmatic. The studies presented here further elucidate both of these mechanisms.

We looked at two distinct aspects of the Far1-independent arrest mechanism. First, we studied the role ...


Role Of Autophagy In Post-Mitotic Midbody Fate And Function: A Dissertation, Tse-Chun Kuo Mar 2013

Role Of Autophagy In Post-Mitotic Midbody Fate And Function: A Dissertation, Tse-Chun Kuo

GSBS Dissertations and Theses

The midbody (MB) is a proteinaceous complex formed between the two daughter cells during cell division and is required for the final cell separation event in late cytokinesis. After cell division, the post-mitotic midbody, or midbody derivative (MBd), can be retained and accumulated in a subpopulation of cancer cells and stem cells, but not in normal diploid differentiated cells. However, the mechanisms by which MBds accumulate and function are unclear. Based on this, I hypothesize that the MBd is degraded by autophagy after cell division in normal diploid differentiated cells, whereas non-differentiated cells have low autophagic ...