SH3YL1 cooperates with ESCRT-I in the sorting and degradation of the EGF receptor

Junya Hasegawa, Jebri Imen, Hikaru Yamamoto, Kazuya Tsujita, Emi Tokuda, Hideki Shibata, Masatoshi Maki, Toshiki Itoh
2019 Journal of Cell Science  
Ubiquitinated membrane proteins such as epidermal growth factor receptor (EGFR) are delivered to early endosomes and then sorted to lysosomes via multivesicular bodies (MVBs) for degradation. The regulatory mechanism underlying formation of intralumenal vesicles en route to generation of MVBs is not fully understood. In this study, we found that SH3YL1, a phosphoinositide-binding protein, had a vesicular localization pattern overlapping with internalized EGF in endosomes in the degradative
more » ... he degradative pathway. Deficiency of SH3YL1 prevents EGF trafficking from early to late endosomes and inhibits degradation of EGFR. Moreover, we show that SH3YL1 mediates EGFR sorting into MVBs in a manner dependent on its C-terminal SH3 domain, which is necessary for the interaction with an ESCRT-I component, Vps37B. Taken together, our observations reveal an indispensable role of SH3YL1 in MVB sorting and EGFR degradation mediated by ESCRT complexes.
doi:10.1242/jcs.229179 pmid:31492760 fatcat:33cchpoxkrhrdapjgwjpaghjce