<p><strong>Abstract</strong></p> <p>RanBPM (Ran-Binding Protein in the Microtubule Organizing Center) is an evolutionarily conserved protein presumed to function as a scaffold in various signal transduction pathways. Null mutations in the <em>Drosophila</em> <em>RanBPM</em> gene cause a pleiotropic effect as seen by the late larval lethality, impaired growth, reduced CNS proliferation and disruption in feeding and response to light behaviours (Scantelbury et al., 2010). We report that<strong> </strong><em>RanBPM</em> mutants display impaired expression and secretion of one of the major <em>Drosophila</em> insulin like peptides, DILP2. Consistent with these findings<strong> </strong><em>RanBPM</em> mutants showed reduced membrane localization of the Phosphatidylinositol (3,4,5)-trisphosphate (PIP3) reporter TGPH (GFP-pleckstrin homology domain (PH) fusion regulated by the Tubulin promoter) and reduced activation of the serine threonine kinase AKT, both read outs of insulin signalling (InS). Ubiquitous overexpression of <em>DILP2</em> partially rescued the reduced larval growth, CNS proliferation and feeding phenotypes caused by <em>RanBPM</em> mutations. Over expression of DILP6 in the glia rescued the reduced CNS proliferation but not the reduced larval growth and feeding behaviour phenotypes. Targeted expression of <em>RanBPM</em> in the fat body suppressed all <em>RanBPM</em> mutant phenotypes except for lethality. In <em>Drosophila</em>, the fat body acts a nutritional sensor involved in coordinating neuroblast proliferation by a TOR- dependent mechanism. Our results present evidence for the role of AKT in the fat body of the <em>RanBPM</em> mutants for the regulation of CNS proliferation, DILP2 secretion, overall growth and feeding</p> / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/15250 |
| Date | 01 September 2014 |
| Creators | Agnihotri, Swati |
| Contributors | Campos, Ana R., Roger Jacobs and Andre Bedard, Biology |
| Source Sets | McMaster University |
| Detected Language | English |
| Type | thesis |
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