Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Marco, S; Neilson, M; Moore, M; Perez-Garcia, A; Hall, H; Mitchell, L; Lilla, S; Blanco, GR; Hedley, A; Zanivan, S; Norman, JC.
Nuclear-capture of endosomes depletes nuclear G-actin to promote SRF/MRTF activation and cancer cell invasion.
Nat Commun. 2021; 12(1):6829
Doi: 10.1038/s41467-021-26839-y
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- Co-Autor*innen der Med Uni Graz
- Rodriguez Blanco Giovanny
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- Abstract:
- Signals are relayed from receptor tyrosine kinases (RTKs) at the cell surface to effector systems in the cytoplasm and nucleus, and coordination of this process is important for the execution of migratory phenotypes, such as cell scattering and invasion. The endosomal system influences how RTK signalling is coded, but the ways in which it transmits these signals to the nucleus to influence gene expression are not yet clear. Here we show that hepatocyte growth factor, an activator of MET (an RTK), promotes Rab17- and clathrin-dependent endocytosis of EphA2, another RTK, followed by centripetal transport of EphA2-positive endosomes. EphA2 then mediates physical capture of endosomes on the outer surface of the nucleus; a process involving interaction between the nuclear import machinery and a nuclear localisation sequence in EphA2's cytodomain. Nuclear capture of EphA2 promotes RhoG-dependent phosphorylation of the actin-binding protein, cofilin to oppose nuclear import of G-actin. The resulting depletion of nuclear G-actin drives transcription of Myocardin-related transcription factor (MRTF)/serum-response factor (SRF)-target genes to implement cell scattering and the invasive behaviour of cancer cells.
- Find related publications in this database (using NLM MeSH Indexing)
- Actins - metabolism
- Active Transport, Cell Nucleus - genetics
- Animals - administration & dosage
- Cell Line, Tumor - administration & dosage
- Cell Nucleus - metabolism
- Cytoplasm - metabolism
- Endosomes - metabolism
- Gene Expression Regulation, Neoplastic - administration & dosage
- Hepatocyte Growth Factor - metabolism
- Humans - administration & dosage
- Mice - administration & dosage
- Mice, Knockout - administration & dosage
- Neoplasm Invasiveness - genetics
- Neoplasms - pathology
- Receptor Protein-Tyrosine Kinases - genetics, metabolism
- Ternary Complex Factors - metabolism