Function of leucine-rich repeat kinase 2 (LRRK2) in endosomal trafficking

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The cell surface is defined by the plasma membrane, which separates the cell interior from the external world. The plasma membrane is studded with proteins that have multiple functions, for example allowing a cell to interact with other cells or to interact with essential cellular nutrients. These proteins are continuously brought into the cell in a process called endocytosis. Following internalization the proteins are delivered to a membrane compartment called endosomes that are a hub for protein sorting. From endosomes the proteins are either targeted for degradation as part of protein renewal or are recycled back to the plasma membrane for continued function. Through these activities endosomes control the levels and localization of a myriad of proteins and thus cell function. This project will examine the function of two specific proteins and how they interact to control key aspects of this fundamental cellular process. There are a large group of scientists, both in Canada and throughout the world that study how proteins are sorted in endosomes. Our work will enhance this field but perhaps more importantly, alterations in these pathways contribute to diseases that are of great concern to Canadians including neurodegenerative diseases and cancer. Our work will lay the foundation for further studies on these important topics.