SH3YL1 cooperates with ESCRT-I in the sorting and degradation of the EGF receptor
SH3YL1 cooperates with ESCRT-I in the sorting and degradation of the EGF receptor
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DOI：
10.1242/jcs.229179
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发表时间：
2019-10-01
影响因子：
4
通讯作者：
Itoh, Toshiki
中科院分区：
文献类型：
--
作者：
Hasegawa, Junya;Jebri, Imen;Itoh, Toshiki
泛素化的膜蛋白，如表皮生长因子受体(EGFR)，被输送到早期的内体，然后通过多泡小体(MVB)分选到溶酶体进行降解。微血管生成过程中腔内小泡形成的调控机制尚不完全清楚。在本研究中，我们发现SH3YL1是一种肌醇磷脂结合蛋白，在降解途径中与内化的EGF在内吞体内具有重叠的囊泡定位模式。SH3YL1的缺失阻止了EGF从早期到晚期的内体转运，并抑制了EGFR的降解。此外，我们发现SH3YL1以一种依赖于其C-末端SH3结构域的方式介导EGFR分类进入MVB，这是与ESCRT-I组分Vps37B相互作用所必需的。综上所述，我们的观察揭示了SH3YL1在ESCRT复合体介导的MVB分选和EGFR降解中发挥着不可或缺的作用。
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 mechanismunderlying 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 intoMVBs 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.