The Actin-binding Protein Moesin and Memory Formation in Drosophila : A thesis presented to Massey University in partial fulfillment of the requirements for the degree of Master of Science in Biochemistry

Abstract

Moesin is a cytoskeletal adaptor protein that plays an important role in modification of the actin cytoskeleton and the formation of dendritic spines, which may be crucial to long-term potentiation. Moesin has also been found to be overexpressed in brains affected by Alzheimer’s disease. Despite being identified as a potential memory gene and linked to several neurological diseases, its role in memory has not been evaluated. The role of Moesin in the Drosophila melanogaster brain was investigated by characterizing the impact of modulating Moesin expression on several aspects of development and behavior. Moesin is involved in both brain and eye development. Knockdown and overexpression of Moesin led to defects in the development of the mushroom body, a brain structure critical for memory formation and recall. Further, knockdown of Moesin throughout development resulted in a significant deficit in long-term memory. Additionally, knockdown of Moesin restricted to adulthood also resulted in a significant deficit in long-term memory, which suggests that Moesin also has a non-developmental role in memory. Further, this requirement for Moesin in long-term memory was traced to the alpha/beta and gamma neurons of the mushroom body. Through the use of a phosphomimetic Moesin mutant that mimics the phosphorylated, activated form of Moesin, the regulation of Moesin in the Drosophila brain was analyzed. Expression of this mutant in neurons disrupted photoreceptor development in the Drosophila eye and a novel sensorimotor phenotype attributed to its expression in the brain was identified resulting in a defect in stereotypical climbing behavior. These results suggest a critical role for Moesin in general neurological functioning and the molecular pathways involved in its activation require further investigation.