The role of lipid phosphatase lnpp5b in the secretory pathway. (360G-Wellcome-079615_Z_06_Z)

Phosphoinositides regulate a number of cellular processes, including membrane traffic, by recruiting various effector proteins to the membrane. Different phosphoinositides are enriched in different compartments, and serve to recruit a specific set of effectors there. In this way phosphoinositides contribute towards giving compartments their functional identity. Lipid kinases and phosphatases modulate phosphoinositide levels and are responsible for maintaining the spatial and temporal regulation of phosphoinositide distribution seen in eukaryotic cells. One such enzyme is Inpp5b, a phosphoinositide phosphatase that is closely related to the OCRL1 protein that is mutated in the X-linked disorder Lowe syndrome. Although Inpp5b has been known for many years, its localisation and function are poorly defined. Recent studies suggest Inpp5b can regulate endocytosis. However, preliminary studies in our lab also suggest a role in the secretory pathway. The aim of this project is to study the precise subcellular localisation of Inpp5b, its interaction with binding partners, and perform functional experiments to evaluate its role in phosphoinositide turnover and membrane dynamics in the secretory pathway. This work will increase our understanding of how phosphoinositides regulate membrane dynamics, and allow us to better appreciate the molecular mechanisms underlying the pathology of Lowe syndrome.