Syntaxin 6-mediated Golgi translocation plays an important role in nuclear functions of EGFR through microtubule-dependent trafficking

Y. Du, J. Shen, J. L. Hsu, Z. Han, M. C. Hsu, C. C. Yang, H. P. Kuo, Y. N. Wang, H. Yamaguchi, S. A. Miller, M. C. Hung

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Receptor tyrosine kinases (RTKs) are cell surface receptors that initiate signal cascades in response to ligand stimulation. Abnormal expression and dysregulated intracellular trafficking of RTKs have been shown to be involved in tumorigenesis. Recent evidence shows that these cell surface receptors translocate from cell surface to different cellular compartments, including the Golgi, mitochondria, endoplasmic reticulum (ER) and the nucleus, to regulate physiological and pathological functions. Although some trafficking mechanisms have been resolved, the mechanism of intracellular trafficking from cell surface to the Golgi is not yet completely understood. Here we report a mechanism of Golgi translocation of epidermal growth factor receptor (EGFR) in which EGF-induced EGFR travels to the Golgi via microtubule-dependent movement by interacting with dynein and fuses with the Golgi through syntaxin 6-mediated membrane fusion. We also demonstrate that the microtubule-and syntaxin 6-mediated Golgi translocation of EGFR is necessary for its consequent nuclear translocation and nuclear functions. Thus, together with previous studies, the microtubule-and syntaxin 6-mediated trafficking pathway from cell surface to the Golgi, ER and the nucleus defines a comprehensive trafficking route for EGFR to travel from cell surface to the Golgi and the nucleus.

Original languageEnglish (US)
Pages (from-to)756-770
Number of pages15
JournalOncogene
Volume33
Issue number6
DOIs
StatePublished - Feb 6 2014
Externally publishedYes

Keywords

  • EGF receptor
  • Golgi and nuclear translocation
  • microtubules
  • syntaxin 6

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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