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Single-molecule imaging reveals the stoichiometry change of epidermal growth factor receptor during transactivation by β2-adrenergic receptor

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Abstract

Stimulation of G protein-coupled receptors (GPCRs) can lead to the transactivation of the epidermal growth factor receptors (EGFR). The cross-communication between the two signaling pathways regulates several important physiological or pathological processes. However, the molecule mechanism underlying EGFR transactivation remains poorly understood. Here, we aim to study the GPCR-mediated EGFR transactivation process using the single-molecule fluorescence imaging and tracking approach. We found that although EGFR existed as monomers at the plasma membrane of resting cells, they became dimers and thus diffused slower following the activation of β2-adrenergic receptor (β2-AR) by isoproterenol (ISO). We further proved that β2-AR-mediated changes of EGFR in stoichiometry and dynamics were mediated by Src kinase. Thus, the observations obtained via the single-molecule imaging and tracking methods shed new insights into the molecular mechanism of EGFR transactivation at single molecule level.

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Acknowledgments

This work was supported by the National Basic Research Program of China (2013CB933701), the National Natural Science Foundation of China (81530009, 21127901, 91213305), and Chinese Academy of Science.

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Authors and Affiliations

  1. Institute of Vascular Medicine of Third Hospital, Ministry of Health Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors and Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100191, China

    Mingliang Zhang, Kangmin He, Jimin Wu, Zijian Li, Han Xiao, Zhizhen Lv & Youyi Zhang

  2. Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructures and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China

    Mingliang Zhang, Kangmin He, Nan Li, Jinghe Yuan, Wei Zhou, Zi Ye & Xiaohong Fang

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  1. Mingliang Zhang
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  2. Kangmin He
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  3. Jimin Wu
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  4. Nan Li
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  6. Wei Zhou
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  10. Zhizhen Lv
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  11. Youyi Zhang
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Correspondence to Youyi Zhang or Xiaohong Fang.

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11426_2017_9072_MOESM1_ESM.pdf

Single-molecule imaging reveals the stoichiometry change of epidermal growth factor receptor during transactivation by β2-adrenergic receptor

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Zhang, M., He, K., Wu, J. et al. Single-molecule imaging reveals the stoichiometry change of epidermal growth factor receptor during transactivation by β2-adrenergic receptor. Sci. China Chem. 60, 1310–1317 (2017). https://doi.org/10.1007/s11426-017-9072-5

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  • DOI: https://doi.org/10.1007/s11426-017-9072-5

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