Clathrin-Independent Endocytosis of ErbB2 in Human Breast Cancer Cells

Endocytosis is an essential cellular process required for functions including nutrient uptake, membrane recycling, and signal transduction. In comparison to the clathrin-mediated pathway, clathrin-independent pathways are poorly understood. New work is now beginning to reveal a picture of multiple non-clathrin pathways. Findings presented in this book identify that ErbB2 is internalized through a non-clathrin pathway in geldanamycin-treated SKBr3 human breast cancer cells. ErbB2 internalization resembled a newly described non-clathrin pathwaytermed the GEEC pathway, a pathway thought to be specific for internalization of GPI-anchored proteins. Suprisingly, ErbB2 and GPI-anchored proteins also co-localized with chimeric fusion proteins containing transmembrane domains, proteins expected to be excluded from the GEEC pathway. Combined with other data from the lab, these results suggest that this pathway is not specific for GPI-anchored proteins and may instead represent a bulk internalization pathway.