Abstract:
: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.
journal_name
FEBS Open Biojournal_title
FEBS open bioauthors
Harwardt MIE,Young P,Bleymüller WM,Meyer T,Karathanasis C,Niemann HH,Heilemann M,Dietz MSdoi
10.1002/2211-5463.12285subject
Has Abstractpub_date
2017-08-29 00:00:00pages
1422-1440issue
9issn
2211-5463pii
FEB412285journal_volume
7pub_type
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