Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 48 for “"ankyrin"”.
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Defining Ankyrin-b Syndrome: Characterization of Ankyrin-b Variants in Mice and Men and the Discovery of a Role for Ankyrin-b in Parasympathetic Control of Insulin Release
<p>Studies in the ankyrin-B+/- mouse reveal that ankyrin-B deficiency is associated with both the benefits of enhanced cardiac contractility and the costs of arrhythmia, early senescence, reduced lifespan, and impaired glucose tolerance. This constellation of traits is known as ankyrin-B syndrome, …
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Obscurin Mediates Ankyrin Complex Formation In The Heart
… Interactions between adaptor proteins such as ankyrins and cytoskeletal proteins such as obscurin play a pivotal role in organizing these functional domains in cardiomyocytes. Therefore, dysfunction of both ankyrin as well as obscurin lead to a host of cardiovascular diseases such as …
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Ankyrin Dependent Mitochondrial Function and Bioenergetics In The Heart
… and tethering wolframin (Wfs-1), a novel ankyrin binding protein along with Inositol Triphosphate Receptor (IP<sub>3</sub>R), Sigma1-R (Sig1R), and Voltage Dependent Anion Channel (VDAC) at MAMs to constitute a Ca<sup>2+</sup> signaling domain.</p> <p>Through a series of cellular …
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Structure/Function Studies on Vps9 domain-containing Ankyrin Repeat protein (VARP)
Vps-9 domain ankyrin repeat protein (Varp) is a widely expressed multi- domain protein of 1050 amino acids that resides in the cytosol. Varp has been shown to be a Rab21 GEF, a Rab32/38 effector and also helps to regulate VAMP7 fusion activity. Varp has more recently been proposed to bind to the …
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Identification and characterization of GRP50 : a novel Golgi-associated ankyrin repeat protein
… of a novel gene, GRP50 (Golgi-associated ankyrin repeat protein of 50 kilodaltons), which encodes a highly conserved mammalian protein exhibiting a unique structural architecture. Homology searching tools reveal that no known orthologues of this protein have been identified in other …
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Investigating The Role Of Transient Receptor Potential Ankyrin One (TRPA1) In Cardiovascular Regulation
TRPAl is a member of the TRP superfamily; localised to neural and non-neuronal sites. TRPAl is activated endogenously by products of oxidative stress, where its expression on sensory neurones leads to the release of vasoactive neuropeptides. Exogenous agonists of TRPAl, mustard oil and …
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Probing the druggability of the Notch1 ankyrin domain using a fragment-based approach
… I report a fragment-based approach to target the ankyrin domain, a historically known but challenging, often-considered “undruggable” target. In this dissertation I describe the application of various biophysical and computational approaches to find, characterise and design compounds. The initial …
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Ankyrin-B and Mtor Complex 1 In The Regulation of Electrical Activities In The Heart
… in the brain and heart is the adaptor protein ankyrin. In the heart, ankyrin-B targets and maintains the membrane expression of ion channels and transporters that are critical for maintaining calcium ion homeostasis, which underlies normal excitation-contraction coupling. Sustained mTORC1 …
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Characterization of the vaccinia virus ankyrin repeat protein K1 on NF-κB inhibition and its contributions to viral pathogenesis
All viruses strategically alter the anti-viral immune response to their benefit. The goal of this thesis was to examine how the vaccinia virus (VACV) K1 protein, which is encoded by the K1L gene, modulates the immune response in vitro and in vivo. In vitro, the K1 protein has multiple …
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Characterization of Novel Substrates of the Tankyrase and RNF146 Destruction Complex and Mechanisms of its Regulation
… 1 and 2, whose domain organization include ankyrin repeat clusters which mediate enzyme-substrate interactions and a SAM domain which regulates oligomerization of Tankyrase into large macromolecular complexes. Tankyrases bind to proteins through a ‘RxxxxG’ peptide motif which facilities …
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Life Under Tension: Computational Studies of Proteins Involved in Mechanotransduction
… bursting. The second set of proteins studied are ankyrin and cadherin repeats, likely forming part of the transduction apparatus in hearing and other mechanical senses. Simulations of all these proteins went beyond the standard approach in which only equilibrium properties are monitored; we …
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Development of peptide inhibitors as molecular therapeutics against tandem-repeat proteins
… TNKS bind their protein substrates through an ankyrin-repeat domain comprising five so-called Ankyrin Repeat Clusters (ARCs). TNKS is of particular therapeutic interest in cancers due to its PARylation of Axin1, a subunit of the β-catenin destruction complex. We investigated the design of …
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Elucidating TRPA1 Ion Channel Aberrations in Oesophageal Adenocarcinoma.
… identified TRPA1 (Transient Receptor Potential Ankyrin 1) as a novel driver gene in OAC with recurrent mutations in a sequenced cohort of 551 OAC patients. TRPA1 is a ligand-gated, Calcium (Ca2+) -permeable membrane protein, which has recently been implicated in breast and prostate cancers. This …
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Gene therapy for axon regeneration
… knockout of the cytoskeletal scaffolding protein Ankyrin-G. Two genetic tools were made and tested to knockout Ankyrin-G: (1) a short hairpin RNA, and (2) a dual promoter AAV viral vector that drives the expression of a CRISPR-associated endonuclease 9 from Staphylococcus aures and one guide RNA …
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Molecular Determinants of TRP Channel Gating
… structure: an intracellular N terminus featuring ankyrin repeats, six transmembrane helices including the pore domain, a re-entrant loop and TRP helix, and an intracellular C terminus with varying structure. Each of these regions has been implicated in the regular function of TRPs, while mutations …
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Acrolein as a novel therapeutic target for spinal cord injury induced neuropathic pain
… directly excites transient receptor potential ankyrin 1 receptor (TRPA1) in DRG nociceptive neurons to transmit pain sensation. In addition, we have observed a significant increase of monocyte chemoattractant protein-1 (MCP1), a pro-inflammatory chemokine that is also known be increased upon …
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MRGX1-TRPAI in inflammatory pain signalling
… the activation of Transient Receptor Potential Ankyrin 1 (TRPA1). TRPA1 activity can be modulated by G-Protein Coupled Receptors (GPCR), leading to sensitisation and hyperalgesia (enhanced pain sensation), typically seen in inflammatory pain conditions. Human Mas-related G-protein-coupled …
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A study of Notch signalling in developmental angiogenesis
… endothelial stalk cell. The Notch-regulated ankyrin repeat protein, Nrarp, is a Notch target gene that is highly expressed in stalk cells and endothelial cells located at vessel branchpoints. Deletion of Nrarp in mouse and morpholino knockdown of nrarp-a and nrarp-b in zebrafish resulted in …
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Nociception and the Experience of Pain Signaling Due to Nerve Damage
… pain, which include Transient Receptor Potential Ankyrin 1 (TRPA1), Transient Receptor Potential Melestatin 8 (TRPM8), and Cannabinoid Receptor 1 (CNR1). We hypothesize through knockdown of TRPA1, TRPM8, or CNR1 gene function may alleviate chronic pain-based behaviors and pain signaling. Gene …
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