Drosophila ALK receptor tyrosine kinase interacts with neurofibromin to regulate learning

Abstract

Event Abstract Back to Event Drosophila ALK receptor tyrosine kinase interacts with neurofibromin to regulate learning Anastasios Moressis1*, Jean Gouzi1 and Efthimios Skoulakis1 1 BSRC "Alexander Fleming", Greece The RAS/RAF/MAPK pathway plays key roles in cognitive processes including learning and memory. Mutations in pathway members result in human syndromes, recognized in a group of phenotypically overlapping disorders, such as neurofibromatosis 1 (NF1), Noonan and Leopard syndromes. Nevertheless, the mechanisms physiologically regulating RAS/RAF/MAPK signalling in adult neurons in vivo are still unclear.We have established a crucial role for the adaptor protein DRK/GRB2 in Drosophila olfactory learning and memory by regulating RAS, RAF and MAPK activities. Expanding on these results, we sought to identify cascade initiating receptor tyrosine kinases (RTKs) expressed in adult Mushroom Bodies, the insect neurons essential for learning and memory, analogous to vertebrate hippocampus. We have identified the highly conserved RTK Anaplastic Lymphoma Kinase-ALK which accumulates preferentially in the dendrites of such neurons and its activation signals through RAS/RAF/MAPK. Activating forms of the receptor or its activating ligand in the adult Drosophila brain, yield learning deficits reminiscent of the cognitive defects of existing Drosophila NF1 models. In contrast, ALK downregulation resulted in enhanced learning. To determine if unregulated ALK signalling results in NF1-associated neuroplasticity deficits, we show that both proteins colocalize in the adult brain. Furthermore we successfully manage to reverse the learning and memory deficits of the Nf1 mutants by limiting ALK activation levels. Finally, we attempt to pharmacologically restore learning in adult Nf1 null flies by administering an ALK inhibitor. In conclusion, using both genetic and pharmacological approaches we propose that ALK is a novel and promising target for treatment of the Neurofibromatosis-1 syndrome. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Moressis A, Gouzi J and Skoulakis E (2009). Drosophila ALK receptor tyrosine kinase interacts with neurofibromin to regulate learning. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.238 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Jun 2009; Published Online: 11 Jun 2009. * Correspondence: Anastasios Moressis, BSRC "Alexander Fleming", Athens, Greece, moressis@fleming.gr Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Anastasios Moressis Jean Gouzi Efthimios Skoulakis Google Anastasios Moressis Jean Gouzi Efthimios Skoulakis Google Scholar Anastasios Moressis Jean Gouzi Efthimios Skoulakis PubMed Anastasios Moressis Jean Gouzi Efthimios Skoulakis Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.