Abstract
Lowe syndrome is an X-linked disorder that is caused by defects in the protein OCRL (Oculocerebrorenal Syndrome of Lowe), a phosphoinositide-5-phosphatase implicated in membrane trafficking, phosphoinositide metabolism, actin dynamics and endocytosis. Despite the fact that OCRL's crystal structure has been solved, the molecular mechanism by which defects in OCRL give rise to Lowe syndrome is not fully understood. Since OCRL is well conserved from mammals to insects, we have used D. melanogaster to recreate a model for Lowe syndrome. We create several site directed-mutations in the single Drosophila homologue of OCRL that disturb important interactions and mimic mutations found in Lowe syndrome patients. We aim to study OCRL's function and subcellular localization by utilizing this insect model for the disease. We found several key amino acids that regulate dOCRL’s capability to bind its partners and control its localization. We hope that in characterizing these conserved residues we are able to shed light on the activity of OCRL to gain a better understanding of Lowe syndrome.