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First published online 3 August 2004
doi: 10.1242/jcs.01233

Journal of Cell Science 117, 4209-4218 (2004)
Published by The Company of Biologists 2004
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Research Article

Sorting nexin 16 regulates EGF receptor trafficking by phosphatidylinositol-3-phosphate interaction with the Phox domain

Jang Hyun Choi1, Won-Pyo Hong1, Myong Jong Kim1, Jae Ho Kim2, Sung Ho Ryu1 and Pann-Ghill Suh1,*

1 Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hojadong, Pohang, Kyungbuk 790-784, Republic of Korea
2 Department of Physiology, College of Medicine, Pusan National University, Pusan 602-739, Republic of Korea

* Author for correspondence (e-mail: pgs{at}postech.ac.kr)

Accepted 23 March 2004

Sorting nexins (SNXs) containing the Phox (PX) domain are implicated in the regulation of membrane trafficking and sorting processes of epithelial growth factor receptor (EGFR). In this study, we investigated whether SNX16 regulates EGF-induced cell signaling by regulating EGFR trafficking. SNX16 is localized in early and recycling endosomes via its PX domain. Mutation of the PX domain disrupted the association between SNX16 and phosphatidylinositol 3-phosphate [PtdIns(3)P]. Treatment with wortmannin, a PtdIns 3-kinase inhibitor, abolished the endosomal localization of SNX16, suggesting that the intracellular localization of SNX16 is regulated by PtdIns 3-kinase activity. SNX16 was found to associate with EGFR after stimulation with EGF in COS-7 cells. Moreover, overexpression of SNX16 increased the rate of EGF-induced EGFR degradation and inhibited the EGF-induced up-regulation of ERK and serum response element (SRE). In addition, mutation in the PX domain significantly blocked the inhibitory effect of SNX16 on EGF-induced activation of ERK and SRE. From these results, we suggest that SNX16 directs the sorting of EGFR to the endosomal compartment and thus regulates EGF-induced cell signaling.

Key words: Sorting nexin (SNX), Epidermal growth factor (EGF), EGF receptor (EGFR), Trafficking, Phosphatidylinositol 3-phosphate (PtdIns(3)P)






© The Company of Biologists Ltd 2004