ABSTRACT
In addition to the lipid components of plasma membrane, super-resolution microscopy can be used to visualize the distribution and organization of membrane proteins. Using direct stochastic optical reconstitution microscopy (dSTORM), another super-resolution microscopic modality (Rust et al. 2006; Heilemann et al. 2008), we can visualize the distribution of the epidermal growth factor (EGF) receptor (EGFR) at the nanoscale. e EGF signaling is involved in diverse physiological processes, and EGFR activation is linked to multiple downstream signaling pathways. Proper regulation of EGF signaling is critical for several biological phenomena, such as survival, proliferation, dierentiation, and locomotion. Aberrant spatiotemporal regulation of its pathway is involved in dierent cancer types (Yarden 2001). Overexpression of EGFR is observed in various types of cancer cells, and hence, drugs that antagonize the EGF signaling pathway have been used as anticancer drugs (Citri and Yarden 2006). e EGFR is localized in the plasma membrane and forms a dimer on EGF binding, which leads to transautophosphorylation of the receptor C-terminal tail. Phosphorylated EGFR forms a signaling complex with downstream adaptor and eector molecules, including Grb2, PLCγ, Shc, and c-Cbl (Bogdan and Klämbt 2001). It has been proposed that EGFR and some downstream molecules co-exist in microdomains before EGF binding, which promotes molecular interaction. Clustering of receptor molecules could also be important for EGFR signaling activated by ligands other than EGF (Linggi and Carpenter 2006) and could control signaling dierences between dierent EGFR/ErbB family members (Lemmon 2009, Sorkin and Goh 2009). Furthermore, the distribution of the receptor in the plasma membrane can be regulated by other factors such as protein-protein interactions. It is also known that microdomains play an important role in EGFR endocytosis on stimulation, which is a major downregulation pathway (Pike et al. 2005). ese molecular interactions are also likely to aect the dynamics of the receptor molecules.
