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Negative Regulation Of The Kinase Lin-45 By The E3/E4 Ubiquitin Ligase Ufd-2, Augustin Deniaud
Negative Regulation Of The Kinase Lin-45 By The E3/E4 Ubiquitin Ligase Ufd-2, Augustin Deniaud
Theses and Dissertations
The serine/threonine kinase BRAF is a key part of the Ras-Raf-MEK-ERK pathway, an inducer of cell growth, differentiation, and survival. In humans, activating mutations, most commonly BRAF(V600E), have been detected in several cancers, including melanoma and thyroid cancer. In the Caenorhabditis elegans ortholog LIN-45, the equivalent mutation LIN-45(V627E) results in elevated Raf-MEK-ERK signaling. We performed an unbiased genetic screen to identify negative regulators of LIN-45(V627E). Here, we report the identification of the E3/E4 ubiquitin ligase UFD-2, and show it is a negative regulator of LIN-45 protein activity and levels. Loss of UFD-2 leads to accumulation of wild-type LIN-45 protein as …
Novel Role Of The Nociceptin System As A Regulator Of Glutamate Transporter Expression In Developing Astrocytes, Logan Meyer
Novel Role Of The Nociceptin System As A Regulator Of Glutamate Transporter Expression In Developing Astrocytes, Logan Meyer
Theses and Dissertations
Our previous results showed that oligodendrocyte development is regulated by both nociceptin and its G-protein coupled receptor, the nociceptin/orphanin FQ receptor (NOPR). The present in vitro and in vivo findings show that nociceptin plays a crucial conserved role in both human and rodent brain astrocytes, regulating the levels of the glutamate/aspartate transporter GLAST/EAAT1. This nociceptin-mediated response takes place during a critical developmental window that coincides with astrocyte maturation and synapse formation. GLAST/EAAT1 upregulation by nociceptin is mediated by NOPR and the downstream participation of a complex signaling cascade that involves the interaction of several kinase systems, including PI-3K/AKT, mTOR and …
Role Of Non-Muscle Myosin Ii And Calcium In Zebrafish Midbrain-Hindbrain Boundary Morphogenesis, Srishti Upasana Sahu
Role Of Non-Muscle Myosin Ii And Calcium In Zebrafish Midbrain-Hindbrain Boundary Morphogenesis, Srishti Upasana Sahu
Theses and Dissertations
Elucidating the molecular mechanisms that play a role in cellular morphogenesis is critical to our understanding of brain development and function. The midbrain-hindbrain boundary (MHB) is one of the first folds in the vertebrate embryonic brain and is highly conserved across species. We used the zebrafish MHB as a model for determining the molecular mechanisms that regulate these cell shape changes. Cellular morphogenesis is tightly regulated by signaling pathways that rearrange the cytoskeleton and produce mechanical forces that enable changes in cell and tissue morphology. The generation of force within a cell often depends on motor proteins, particularly non-muscle myosins …
The Role Of Gap-43 Phosphorylation In Axon Behavior In The Developing Zebrafish Visual System, Jennifer Forecki
The Role Of Gap-43 Phosphorylation In Axon Behavior In The Developing Zebrafish Visual System, Jennifer Forecki
Theses and Dissertations
Developing neurons extend processes to specific targets and establish connections that are essential for future function of the nervous system. One of these processes, the axon, has a motile tip called a growth cone that rearranges its membrane-associated actin cytoskeleton to turn toward or away from environmental guidance cues. Growth associated protein 43 (GAP-43) is one of the most abundant proteins associated with axonal growth cone membranes and is known to modulate the formation and stability of the actin cytoskeleton during axon guidance. Protein kinase C (PKC)-mediated phosphorylation of GAP-43 on serine 42 regulates its interactions with actin. Phosphorylated GAP-43 …
Novel Role Of Mecp2 In Developing Oligodendrocytes And Myelination, Daniel Moore
Novel Role Of Mecp2 In Developing Oligodendrocytes And Myelination, Daniel Moore
Theses and Dissertations
Methyl-CpG-binding protein 2 (MeCP2 is) is an epigenetic regulator that binds to methylated DNA. Initially identified as transcriptional repressor, MeCP2 also binds to different proteins functioning as gene activator. Importantly, MecCP2 gene mutations and changes in MeCP2 levels are associated to several forms of mental retardation and autism-related disorders; including Rett, a neurodevelopmental disorder affecting primarily girls. While brain MeCP2 was considered to be exclusively neuronal, this regulator is also present in glia. We found that oligodendrocytes, the myelinating cells of the central nervous system (CNS), express particularly high MeCP2 levels at a developmental stage that precedes their final maturation. …
A Study On The Biochemical And Cellular Effects Of Enviormental Tobacco Smoke On Adult And Developing Rat Brain Biochemistry, Brian Fuller
A Study On The Biochemical And Cellular Effects Of Enviormental Tobacco Smoke On Adult And Developing Rat Brain Biochemistry, Brian Fuller
Theses and Dissertations
Exposure to environmental tobacco smoke (ETS) has been recognized as a significant health risk for adults and children. In adults, ETS exposure has been linked to increased incidences of cardiovascular disease and dementia. In children, exposure has been linked to behavioral and cognitive deficits. Studies on the effects of ETS in the brain have been largely epidemiological, and have lacked a defined explanation of the molecular/biochemical effects of ETS. The present dissertation aims to test whether ETS exposure leads to altered biochemistry in the adult and developing mammalian brain. A rat ETS exposure model was employed to investigate changes at …