The Library
Molecular mechanisms of selective autophagy in innate immunity.
Tools
Tools
Tools
Tusco, Radu (2017) Molecular mechanisms of selective autophagy in innate immunity. PhD thesis, University of Warwick.
|
PDF
WRAP_Theses_Tusco_2017.pdf - Submitted Version - Requires a PDF viewer. Download (110Mb) | Preview |
Official URL: http://webcat.warwick.ac.uk/record=b3110360~S15
Abstract
Autophagy is an evolutionarily conserved process of cellular material degradation, involved in development, starvation-induced nutrient-level control, degradation of aggregated proteins and pathogen removal. The specificity of this process is governed by selective autophagy receptors, messenger proteins which identify cargo and deliver it to Atg8a – a component of the core autophagic machinery. Receptors bind to Atg8-family proteins via the LIR motif, a short amino-acid sequence that is conserved across the animal kingdom.
We performed a bioinformatics screen in order to identify new putative Atg8a interacting proteins. We searched the Drosophila proteome for proteins containing LIRmotifs and ubiquitin-binding domains. We identified the protein Kenny (homologue of human IKKg), which contains a LIR motif and a conserved UBAN domain.
Kenny is a modulator of the Drosophila Immune deficiency (IMD) pathway, an innate immunity response targeted at gram-negative bacteria. Using biochemical approaches and in vivo studies in Drosophila we observed that Kenny interacted directly with Atg8a via its LIR motif and was selectively degraded by autophagy. We found that Kenny accumulated in autophagy depleted flies, which was accompanied by a constitutive activation of the IMD pathway and expression of antimicrobial peptides.This caused a hyperproliferation of stem cells in the midgut, reduced defecation rates and shortened the overall fly lifespan.
Given sequence similarities between Kenny and another described receptor, Optineurin, we also investigated Kenny’s potential role in mitophagy and/or xenophagy. Kenny accumulated and localised with mitochondria in thorax muscles of flies, treated with FCCP. Kenny was found to localise in the vicinity of phagocytosed Staphylococcus aureus in larval haemocytes, cultured ex vivo. We propose that Optineurin could be a new functional mammalian orthologue of Kenny, in addition to the established mammalian homologue, NEMO.
| Item Type: | Thesis (PhD) | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > QH Natural history > QH301 Biology | ||||
| Library of Congress Subject Headings (LCSH): | Cellular control mechanisms, Drosophila -- Physiological aspects, Immunodeficiency, Peptide antibiotics | ||||
| Official Date: | August 2017 | ||||
| Dates: |
|
||||
| Institution: | University of Warwick | ||||
| Theses Department: | School of Life Sciences | ||||
| Thesis Type: | PhD | ||||
| Publication Status: | Unpublished | ||||
| Supervisor(s)/Advisor: | Johansen, Terje,1969- ; Jacomin, Anne-Claire, 1987- | ||||
| Extent: | xix, 210 leaves : illustrations, charts. | ||||
| Language: | eng |
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
