SH3YL1 cooperates with ESCRT-I in the sorting and degradation of the EGF receptor.
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 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.
['Hasegawa|Junya|J|', 'Jebri|Imen|I|', 'Yamamoto|Hikaru|H|', 'Tsujita|Kazuya|K|', 'Tokuda|Emi|E|', 'Shibata|Hideki|H|', 'Maki|Masatoshi|M|', 'Itoh|Toshiki|T|0000-0001-6433-1894']
D002460:Cell Line D004705:Endocytosis D056827:Endosomal Sorting Complexes Required for Transport D011992:Endosomes D004815:Epidermal Growth Factor D066246:ErbB Receptors D006367:HeLa Cells D006801:Humans D047468:Immunoprecipitation D008247:Lysosomes D008565:Membrane Proteins D008856:Microscopy, Fluorescence D057146:Multivesicular Bodies D011485:Protein Binding D000072417:Protein Domains D021381:Protein Transport D034622:RNA Interference D022161:Transport Vesicles
SH3YL1 EGF Endosome MVB ESCRT