Inhibitory regulation of EGF receptor degradation by sorting nexin 5.
Endosomal trafficking of EGF receptor (EGFR) upon stimulation is a highly regulated process during receptor-mediated signaling. Recently, the sorting nexin (SNX) family has emerged as an important regulator in the membrane trafficking of EGFR. Here, we report the identification of a novel interaction between two members of the family, SNX1 and SNX5, which is mediated by the newly defined BAR domain of both SNXs. We have also shown that the PX domain of SNX5 binds specifically to PtdIns other than to PtdIns(3)P. Furthermore, the BAR domain but not the PX domain of SNX5 is sufficient for its subcellular membrane association. Functionally, overexpression of SNX5 inhibits the degradation of EGFR. This process appears to be independent of its interaction with SNX1. However, overexpression of SNX1 is able to attenuate the effect of SNX5 on EGFR degradation, suggesting the two proteins may play antagonistic roles in regulating endosomal trafficking of the receptor.
Liu
Hao
H
Department of Neurology and Neurobiology, University of Pittsburgh School of Medicine, W958 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
Liu
Zu-Qiang
ZQ
Chen
Carol X-Q
CX
Magill
Stephen
S
Jiang
Yu
Y
Liu
Yong-Jian
YJ
D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes; D009154:Mutation; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary; D051381:Rats; D058305:Sorting Nexins; D014162:Transfection; D033921:Vesicular Transport Proteins / Q000378:metabolism / Q000502:physiology
D002352:Carrier Proteins; D008081:Liposomes; D018129:Phosphatidylinositol Phosphates; C402667:SNX5 protein, human; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; C055525:phosphatidylinositol 3-phosphate; D066246:ErbB Receptors