TRE17/USP6 regulates ubiquitylation and trafficking of cargo proteins that enter cells by clathrin-independent endocytosis.

نویسندگان

  • Yuji Funakoshi
  • Margaret M Chou
  • Yasunori Kanaho
  • Julie G Donaldson
چکیده

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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عنوان ژورنال:
  • Journal of cell science

دوره 127 Pt 21  شماره 

صفحات  -

تاریخ انتشار 2014