Deletion of integrin linked kinase in endothelial cells results in defective 
RTK signaling caused by caveolin 1 mislocalization

Malan, D.; Elischer, A.; Hesse, M.; Wickström, S. A.; Fleischmann, B. K.; Bloch, W.

doi:10.1242/dev.091298

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Deletion of integrin linked kinase in endothelial cells results in defective RTK signaling caused by caveolin 1 mislocalization

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Wickström, S. A.
Wickström – Skin Homeostasis and Ageing, Max Planck Research Groups, Max Planck Institute for Biology of Ageing, Max Planck Society;

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http://www.ncbi.nlm.nih.gov/pubmed/23404105
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Citation

Malan, D., Elischer, A., Hesse, M., Wickström, S. A., Fleischmann, B. K., & Bloch, W. (2013). Deletion of integrin linked kinase in endothelial cells results in defective RTK signaling caused by caveolin 1 mislocalization. Development, 140(5), 987-95. doi:10.1242/dev.091298.

Cite as: https://hdl.handle.net/21.11116/0000-000B-8151-7

Abstract

Integrin linked kinase (ILK) connects the ILK-Pinch-Parvin complex with integrin adhesion sites. Because of the functional relevance of integrin-linked signaling for endothelial cell (EC) biology, we have explored this pathway in Ilk(-/-) embryonic stem (ES) cells differentiated into ECs and vessel-like structures. We have focused in particular on the mechanistic relevance of ILK-Pinch-Parvin complex-related signaling for EC development and tube formation. Our analysis revealed that the formation of vessel-like structures was strongly reduced in Ilk(-/-) ES cells and that this phenotype could be rescued by re-expression of ILK in ES cells. ECs were MACS sorted from wild-type (WT) and Ilk(-/-) ES cells and functional analysis using intracellular calcium imaging as the read-out yielded a complete lack of vascular endothelial growth factor- and epidermal growth factor-dependent responses. The possibility of a caveolin 1-related defect was investigated by transfecting WT and Ilk(-/-) ECs with a caveolin 1-EGFP fusion protein. Time-lapse microscopy showed that the prominent phenotype is due to altered dynamics of caveolin 1 and to a lack of positioning of caveolin 1 in the vicinity of the plasma membrane and that it is rescued by re-expressing ILK in the Ilk(-/-) ES cells. We also found that the defect is caused by the perturbed organization of microtubules and cortical actin filaments. Thus, ILK is required as a scaffold to allow actin-microtubule interactions and correct positioning of caveolin 1 close to the plasma membrane. This is crucial for signaling compartmentalization in ECs and explains the key role of ILK for EC development and function.