SNX25 regulates TGF-β signaling by enhancing the 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-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.
Department of Hematology/Oncology, Affiliated Hospital, Hainan Medical College, Hainan (570102), China.
Xinbao
X
Hao
Yinyin
Y
Wang
Fangli
F
Ren
Shanshan
S
Zhu
Yongming
Y
Ren
Baoqing
B
Jia
Yi-Ping
YP
Li
Yuguang
Y
Shi
Zhijie
Z
Chang
D000818:Animals; D045744:Cell Line, Tumor; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D051379:Mice; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism*; D015398:Signal Transduction; D058305:Sorting Nexins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D002966:Clathrin; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; C517049:SNX25 protein, human; D058305:Sorting Nexins; D016212:Transforming Growth Factor beta