SNX25 regulates TGF-β signaling by enhancing the receptor degradation

Xinbao Hao, Yinyin Wang, Fangli Ren, Shanshan Zhu, Yongming Ren, Baoqing Jia, Yi Ping Li, Yuguang Shi, Zhijie Chang

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

SNXs (sorting nexin), a family of proteins playing roles in cargo sorting and signaling from compartments within the endocytic network, regulate traffic of membrane proteins including TGF-β receptors. Here we report that the full length human and mouse SNX25, a SNX member with PX, PXA and RGS domains, co-localizes with TGF-β receptors, and forms internalized cytosolic punctae upon treatment with TGF-β While overexpression of SNX25 inhibits TGF-β induced luciferase reporter activity, knocking down endogenous SNX25 by siRNA in NIH3T3 cells elevates the TGF-β receptor levels and facilitates TGF-β signaling. Immunoprecipitation experiments demonstrate that SNX25 interacts with TβRI. Western blot analyses indicate that SNX25 enhances the degradation of TGF-β receptors. SNX25 induced TGF-β receptor degradation is shown via the clathrin dependent endocytosis pathway into lysosome. We have characterized that PXA domain of SNX25 is required for the degradation of TβRI. Our findings demonstrate that SNX25 negatively regulates TGF-β signaling by enhancing the receptor degradation through lysosome pathway.

Original languageEnglish (US)
Pages (from-to)935-946
Number of pages12
JournalCellular Signalling
Volume23
Issue number5
DOIs
StatePublished - May 1 2011
Externally publishedYes

Keywords

  • Endocytosis
  • Receptor degradation
  • SNX25
  • Sorting nexin
  • TGF-beta

ASJC Scopus subject areas

  • Cell Biology

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