Abstract:  Endosomal recycling is an essential cellular process in maintaining the homeostasis of plasma membrane (PM) proteins crucial for cell signaling and survival. This process is regulated by the cargo sorting complex Retriever, which directs specific endocytosed PM proteins (cargoes) from endosomes back to the cell membrane. Comprising VPS35L, VPS26C, and VPS29, Retriever partners with various protein assemblies, including the COMMD-CCDC22-CCDC93 (CCC) complex for endosomal lipid regulation, the sorting nexin SNX17 for cargo recognition, and the WASH complex for endosomal actin polymerization. The mechanisms underlying Retriever assembly and its interactions with regulatory factors have remained elusive. I will present our recent progress in understanding the structural mechanisms governing Retriever assembly and its interaction with CCC and SNX17. This knowledge provides insight into how these protein assemblies direct endosomal recycling and how mutations may be connected to diseases, such as cancers and neurodevelopmental disorders.

The Bio-WIP Seminars (formerly BBMB WIP seminars) are sponsored by the BBMB Graduate Learning Community.