Data and code from: Tetraspanin CD82 shapes EGFR signaling outcomes through nanoscale receptor organization

Tetraspanins are integral membrane proteins that play a crucial role in
organizing and regulating cellular signaling by serving as scaffolds that
compartmentalize receptors and other signaling molecules within membrane
microdomains. Here, we report how the tetraspanin CD82 modulates the
molecular organization and signaling of the Epidermal Growth Factor
Receptor (EGFR), a key molecule involved in cellular proliferation,
differentiation, and survival. Combining multi-color super-resolution
microscopy with advanced image reconstruction and analysis techniques, we
demonstrate that CD82 selectively associates with EGFR, promotes receptor
oligomerization, and acts as a regulator of ligand-independent receptor
phosphorylation in a palmitoylation-dependent manner. Additionally, CD82
promotes a more compact molecular organization of EGFR, which correlates
with altered endocytosis and downstream signaling outcomes. These findings
underscore the importance of tetraspanins in the spatial and functional
regulation of cell surface receptors, with implications for controlling
aberrant signaling in disease and positions CD82 as a potential target for
developing therapeutic strategies aimed at modulating EGFR signaling by
influencing receptor organization.