Dimerization drives EGFR endocytosis through two sets of compatible endocytic codes

作者：Wang Qian; Chen Xinmei; Wang Zhixiang^*

来源：Journal of Cell Science, 2015, 128(5): 935-950.

DOI：10.1242/jcs.160374

• EGF receptor
• Endocytosis
• Dimerization
• Dual endocytic codes

We have shown previously that epidermal growth factor (EGF) receptor (EGFR) endocytosis is controlled by EGFR dimerization. However, it is not clear how the dimerization drives receptor internalization. We propose that EGFR endocytosis is driven by dimerization, bringing two sets of endocytic codes, one contained in each receptor monomer, in close proximity. Here, we tested this hypothesis by generating specific homo- or hetero-dimers of various receptors and their mutants. We show that ErbB2 and ErbB3 homodimers are endocytosis deficient owing to the lack of endocytic codes. Interestingly, EGFR-ErbB2 or EGFR-ErbB3 heterodimers are also endocytosis deficient. Moreover, the heterodimer of EGFR and the endocytosis-deficient mutant EGFR Delta 1005-1017 is also impaired in endocytosis. These results indicate that two sets of endocytic codes are required for receptor endocytosis. We found that an EGFR-PDGFR beta heterodimer is endocytosis deficient, although both EGFR and PDGFR beta homodimers are endocytosis-competent, indicating that two compatible sets of endocytic codes are required. Finally, we found that to mediate the endocytosis of the receptor dimer, the two sets of compatible endocytic codes, one contained in each receptor molecule, have to be spatially coordinated.

• 出版日期2015-3-1