title: Syntaxin 6-mediated Golgi translocation plays an important role in nuclear functions of EGFR through microtubule-dependent trafficking.
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.
authors: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors: Y
authors: Y
authors: Du
authors: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors: J
authors: J
authors: Shen
authors: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung, Taiwan [3] Department of Biotechnology, Asia University, Taichung, Taiwan.
authors: J L
authors: JL
authors: Hsu
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Z
authors: Z
authors: Han
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: M-C
authors: MC
authors: Hsu
authors: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors: C-C
authors: CC
authors: Yang
authors: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA.
authors: H-P
authors: HP
authors: Kuo
authors: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung, Taiwan [3] Department of Biotechnology, Asia University, Taichung, Taiwan.
authors: Y-N
authors: YN
authors: Wang
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: H
authors: H
authors: Yamaguchi
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: S A
authors: SA
authors: Miller
authors: 1] Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA [3] Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung, Taiwan [4] Department of Biotechnology, Asia University, Taichung, Taiwan.
authors: M-C
authors: MC
authors: Hung
mesh_terms: D002465:Cell Movement / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D004398:Dyneins / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D021381:Protein Transport; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics
chemical_list: D050765:Qa-SNARE Proteins; D034741:RNA, Small Interfering; D066246:ErbB Receptors; D004398:Dyneins
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