National Institute of General Medical Sciences 5R35GM150960-04

Molecular mechanisms of endocytic initiation and cargo selection

Research project funded by the National Institute of General Medical Sciences to study molecular mechanisms of endocytic initiation and cargo selection, with implications for disease and drug development.

Description

Clathrin-mediated endocytosis (CME) is the primary route of internalization from the plasma membrane, essential for cell viability and response to extracellular cues like growth factor signaling. Mutations in the endocytic machinery or regulatory proteins lead to diseases such as cancer and neurodegeneration. This research aims to understand the mechanisms of endocytic initiation and cargo selection, focusing on AP2 clathrin adaptor complex, membrane-induced allostery, and regulatory conformations. The study will utilize cryo-EM, biochemical reconstitution, and single-molecule fluorescence microscopy in a membrane environment to develop mechanistic models relevant to disease and drug development.

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