[Truncated abstract] Neuregulins (NRG’s) are pleiotropic growth factors that participate in a wide range of biological processes. The family of membrane-bound growth factors bind to and activate ErbB receptors on adjacent target cells, mediating multiple biological processes. NRG-1, NRG-2 and NRG-3 are all highly expressed in the nervous system, where it has been shown that NRG-1 is important for neuronal development, migration, synapse formation and glial cell proliferation. Little is known, however, on the specific roles of NRG-2 and NRG-3, although it is apparent that despite similar expression patterns and overlapping receptor specificity, NRG-2 and NRG-3 do not compensate for the loss of NRG-1 and mediate their own distinct activities. … Subcellular localisation experiments showed that this domain is important for trafficking of the fulllength protein to various intracellular compartments in an activity dependent manner. In addition, the ICD is required to elicit a cell death response in cultured cells and provoke an elevated α-amino-3-hydroxyl-5-methylisoxazole-4-propionate (AMPA) response in organotypic neuronal cultures following transient expression of NRG-3. A yeast two-hybrid screen identified 14-3-3ζ and PICK1 as two proteins that interacte with the human NRG-3 ICD. These interactions were confirmed both in vitro and in vivo, and were further characterised at a molecular level. This study demonstrates the ability of NRG-3 to mediate signal transduction through a biologically active ICD; a conclusion supported by identifying cytoplasmic proteins that interact with the ICD. These observations point to an additional layer of complexity where bi-directional signalling contributes to the full repertoire of NRG-3 functions.

[Truncated abstract] A range of biotic and abiotic stresses increase levels of reactive oxygen species (ROS) in plants due to perturbations of chloroplast and mitochondrial metabolism and the generation of ROS in defence responses. The polyunsaturated fatty acids of membrane lipids are susceptible to ROS induced peroxidation yielding various aldehydes, alkenals and hydroxyalkenals including the cytotoxic compound 4-hydroxy- 2-nonenal (HNE). HNE has the potential to cause substantial oxidative damage in cells via its reactivity with sulfhydryl groups of cysteine (Cys) and lipoic acid, the imidazole group of histidine (His) and the ?-amino group of lysine (Lys) protein residues. Analysis of the components of the plant respiratory electron transport chain to HNE revealed a particular susceptibility to inhibition of activity of the alternative oxidase (Aox). Incubation with HNE prevented dimerisation of Aox protein, suggesting that one site of modification was the conserved cysteine residue involved in dimerisation and activation of this enzyme (Cys1). However, a naturally occurring isoform of Aox lacking Cys1 and unable to dimerise, LeAox1b from tomato, was equally sensitive to HNE inhibition, showing that other amino acid residues in Aox also interact with HNE and are likely responsible for inactivation of the enzyme. ... The broader impact of HNE on the whole Arabidopsis mitochondrial proteome was examined by use of various 2-dimensional gel separation techniques coupled with use of HNE-adduct antibodies. 32 proteins involved in a number of mitochondrial functions were found to be susceptible to modification by HNE, including components of the electron transport chain, the TCA cycle, as well as proteins involved amino acid metabolism and stress-responses. Implications of modification of these proteins by HNE are discussed. As HNE is produced in vivo during oxidative stress, the profile of mitochondrial targets of HNE was examined from Arabidopsis cell cultures exposed to various oxidative stress inducers. Menadione and hydrogen peroxide induced oxidative stress throughout the cell, while antimycin A initiated a mitochondrial targeted stress. A differential profile of mitochondrial proteins was observed to be modified by HNE in the various treatments. These results also showed that induction of stress within a whole cell can impact lipid peroxidation within the mitochondria. Overall, this work showed the presence and production of HNE in plant cells, and that HNE, both exogenous and endogenous, has the ability to modify a specific subset of mitochondrial proteins. In several cases this HNE modification was shown to have functional or structural consequences.

Thesis (Ph. D.)--University of Texas at Austin, 2008. / Vita. Includes bibliographical references.

Thesis (Ph.D.)--University of Western Australia, 2007.

Thesis (Ph. D.)--Virginia Polytechnic Institute and State University, 1993. / Vita. Abstract. Includes bibliographical references (leaves 187-190). Also available via the Internet.

Thesis (Ph.D.)--Flinders University, School of Medicine, Dept. of Clinical Pharmacology. / Typescript bound. Includes bibliographical references: (leaves 334-391) Also available electronically.

Thesis (Ph. D.)--University of Alberta, 2009. / Title from pdf file main screen (viewed on July 23, 2009). "A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Department of Cell Biology, University of Alberta." Includes bibliographical references.

Thesis (Ph.D.)--University of Alberta, 2010. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Centre of Neuroscience. Title from pdf file main screen (viewed on April 18, 2010). Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri-Columbia, 2002. / Typescript. Vita. Includes bibliographical references (leaves 199-213). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2002. / Typescript. Vita. Includes bibliographical references (leaves 199-213). Also available on the Internet.