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Contraction of endothelial cells: 40 years of research, but the debate still lives

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Abstract

Force generation in non-muscle cells is vital for many cellular and tissue functions. Force-generating mechanisms include actomyosin-mediated contraction, actin polymerization that drives plasma membrane protrusions and filopodia as well as kinesin- and dynein-controlled transport of vesicles and organelles along the microtubule cytoskeleton. The actomyosin-mediated contractility and actin remodeling in both epithelium and endothelium were shown to have significant impact on cell migration, shape change and formation and control of intercellular junctions. In endothelium, contraction is supposed to control permeability for fluid and solutes. However, recent studies demonstrated the constitutive appearance of junction-associated intermittent lamellipodia (JAIL) that drive vascular endothelial cadherin (VE-cadherin) dynamics and control endothelial permeability. Since thrombin blocks JAIL formation and thus increases endothelial permeability, the concept of a simple Rho GTPase-controlled contraction, which is supposed to open endothelial junctions, becomes challenged. Furthermore, specific tyrosine phosphorylation sites of VE-cadherin and catenins have been shown to be involved in control of VE-cadherin-mediated cell adhesion. How the causal–mechanistic interdependency between contractility, VE-cadherin and catenin phosphorylation and JAIL-mediated dynamic remodeling of VE-cadherin is regulated is still an open question and needs to be further addressed.

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  1. Cited from Dallos, P. and B. Fakler (2002). Prestin, a new type of motor protein. Nat Rev Mol Cell Biol 3(2): 104–111.

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Acknowledgments

This work was supported by grants from the German Research Council to H.S. (DFG INST 2105/24–1 and SCHN 430/6–2), the Excellence Cluster Cells In Motion (CIM), and WWU-Münster flexible fund to H.S (FF-2014-15).

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Correspondence to Hans Schnittler.

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This short overview is dedicated to D. Drenckhahn.

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Schnittler, H. Contraction of endothelial cells: 40 years of research, but the debate still lives. Histochem Cell Biol 146, 651–656 (2016). https://doi.org/10.1007/s00418-016-1501-0

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