期刊
JOURNAL OF CELL SCIENCE
卷 127, 期 21, 页码 4750-4761出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.156786
关键词
TRE17; USP6; Ubiquitin; Cargo sorting; Ubiquitin-specific protease; Lysosome
类别
资金
- Intramural Research Program in the National Heart, Lung and Blood Institute at the National Institutes of Health [HL006060]
- National Cancer Institute [CA126452]
- Ministry of Education, Science, Sports and Culture of Japan [26440044]
- Grants-in-Aid for Scientific Research [26440044] Funding Source: KAKEN
Plasma membrane proteins that enter cells by clathrin-independent endocytosis (CIE) are sorted either to lysosomes for degradation or recycled back to the plasma membrane. Expression of some MARCH E3 ubiquitin ligases promotes trafficking of CIE cargo proteins to lysosomes by ubiquitylating the proteins. Here, we show that co-expression of the ubiquitin-specific protease TRE17/USP6 counteracts the MARCH-dependent targeting of CIE cargo proteins, but not that of transferrin receptor, to lysosomes, leading to recovery of the stability and cell surface level of the proteins. The ubiquitylation of CIE cargo proteins by MARCH8 was reversed by TRE17, suggesting that TRE17 leads to deubiquitylation of CIE cargo proteins. The effects of TRE17 were dependent on its deubiquitylating activity and expression of TRE17 alone led to a stabilization of surface major histocompatibility complex class I (MHCI) molecules, a CIE cargo, suggesting that deubiquitylation of endogenous CIE cargo proteins promotes their stability. This study demonstrates that cycles of ubiquitylation and deubiquitylation can determine whether CIE cargo proteins are degraded or recycled.
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