Single-Molecule Super-Resolution Microscopy Reveals Heteromeric Complexes of MET and EGFR upon Ligand Activation

International Journal of Molecular Sciences

Sebastian Strauss¹  Ralf Jungmann¹  Mike Heilemann²  Petra Freund²  Yunqing Li²  Marie-LenaI.E. Harwardt²  MarinaS. Dietz²  MarkS. Schröder²  Sebastian Malkusch²  Shashi Gupta³  Nebojsa Janjic³ 

[1] Department of Physics and Center for Nanoscience, Ludwig Maximilian University, 80539 Munich, Germany;Single Molecule Biophysics, Institute of Physical and Theoretical Chemistry, Goethe University Frankfurt, Max-von-Laue-Str. 7, 60438 Frankfurt, Germany;SomaLogic, Inc., Boulder, CO 80301, USA;

关键词: receptor tyrosine kinases;    MET;    EGFR;    receptor cross-interaction;    single-molecule localization microscopy;    single-particle tracking;   

DOI  :  10.3390/ijms21082803

来源: DOAJ

【 摘 要 】

Receptor tyrosine kinases (RTKs) orchestrate cell motility and differentiation. Deregulated RTKs may promote cancer and are prime targets for specific inhibitors. Increasing evidence indicates that resistance to inhibitor treatment involves receptor cross-interactions circumventing inhibition of one RTK by activating alternative signaling pathways. Here, we used single-molecule super-resolution microscopy to simultaneously visualize single MET and epidermal growth factor receptor (EGFR) clusters in two cancer cell lines, HeLa and BT-20, in fixed and living cells. We found heteromeric receptor clusters of EGFR and MET in both cell types, promoted by ligand activation. Single-protein tracking experiments in living cells revealed that both MET and EGFR respond to their cognate as well as non-cognate ligands by slower diffusion. In summary, for the first time, we present static as well as dynamic evidence of the presence of heteromeric clusters of MET and EGFR on the cell membrane that correlates with the relative surface expression levels of the two receptors.

【 授权许可】

Unknown