Tetraspanin CD82 Regulation of EGFR Organization and Signaling

The regulation of intermolecular interactions is essential for orchestrating complex cellular processes. By modulating molecular interactions at the interface between the intracellular and extracellular space, the tetraspanin proteins control diverse processes fundamental to the biology of multicellular life, including cell adhesion and signaling. The epidermal growth factor receptor (EGFR) is a key player in myriad developmental and pathological processes, and the receptor’s spatial organization underlies its ability to signal. Here, we use super-resolution microscopy to study the mechanisms by which tetraspanin CD82 regulates EGFR organization and signaling. We find that CD82-EGFR interactions play a critical role in regulating the receptor’s activation and modulating downstream outcomes. Additionally, we identify a role for EGFR in Acute Myeloid Leukemia, where the receptor promotes the survival of leukemia cells following chemotherapy. Collectively, our findings emphasize the importance of studying the regulation of molecular interactions to further our understanding of cell biology and human health.