Membrane dynamics of resting and internalin B‐bound MET receptor tyrosine kinase studied by single‐molecule tracking

  • The human MET receptor tyrosine kinase contributes to vertebrate development and cell proliferation. As a proto‐oncogene, it is a target in cancer therapies. MET is also relevant for bacterial infection by Listeria monocytogenes and is activated by the bacterial protein internalin B. The processes of ligand binding, receptor activation, and the diffusion behavior of MET within the plasma membrane as well as its interconnections with various cell components are not fully understood. We investigated the receptor diffusion dynamics using single‐particle tracking and imaging fluorescence correlation spectroscopy and elucidated mobility states of resting and internalin B‐bound MET. We show that internalin B‐bound MET exhibits lower diffusion coefficients and diffuses in a more confined area in the membrane. We report that the fraction of immobile receptors is larger for internalin B‐bound receptors than for resting MET. Results of single‐particle tracking in cells treated with various cytotoxins depleting cholesterol from the membrane and disrupting the actin cytoskeleton and microtubules suggest that cholesterol and actin influence MET diffusion dynamics, while microtubules do not have any effect.

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Author:Marie-Lena I. E. Harwardt, Phoebe Young, Willem M. Bleymüller, Timo Meyer, Christos Karathanasis, Hartmut H. Niemann, Mike HeilemannORCiDGND, Marina DietzORCiDGND
Pubmed Id:
Parent Title (English):FEBS Open Bio
Publisher:Elsevier on behalf of the Federation of European Biochemical Societies
Place of publication:Cambridge
Document Type:Article
Year of Completion:2017
Date of first Publication:2017/08/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/04/26
Tag:MET receptor; diffusion dynamics; endocytosis; internalin B; receptor tyrosine kinases; single‐molecule tracking
Page Number:19
First Page:1422
Last Page:1440
© 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
Open-Access-Publikationsfonds:Biochemie, Chemie und Pharmazie
Licence (German):License LogoCreative Commons - Namensnennung 4.0