SNX25 regulates TGF-beta signaling by enhancing the receptor degradation

作者：Hao, Xinbao; Wang, Yinyin; Ren, Fangli; Zhu, Shanshan; Ren, Yongming; Jia, Baoqing; Li, Yi-Ping; Shi, Yuguang; Chang, Zhijie^*

来源：Cellular Signalling, 2011, 23(5): 935-946.

DOI：10.1016/j.cellsig.2011.01.022

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

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-beta receptors. Here we report that the full length human and mouse SNX25, a SNX member with PX, PXA and RGS domains, colocalizes with TGF-beta receptors, and forms internalized cytosolic punctae upon treatment with TGF-beta. While overexpression of SNX25 inhibits TGF-beta induced luciferase reporter activity, knocking down endogenous SNX25 by siRNA in NIH3T3 cells elevates the TGF-beta receptor levels and facilitates TGF-beta signaling. Immunoprecipitation experiments demonstrate that SNX25 interacts with T beta RI. Western blot analyses indicate that SNX25 enhances the degradation of TGF-beta receptors. SNX25 induced TGF-beta 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 T beta RI. Our findings demonstrate that SNX25 negatively regulates TGF-beta signaling by enhancing the receptor degradation through lysosome pathway.

• 出版日期2011-5
• 单位清华大学; 中国人民解放军总医院; 膜生物学国家重点实验室; 海南医学院