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Review
. 2014 Mar 25:2:11-21.
doi: 10.2147/HP.S53575. eCollection 2014.

Hypoxia and the modulation of the actin cytoskeleton - emerging interrelations

Anke Zieseniss  1
Affiliations
Review

Hypoxia and the modulation of the actin cytoskeleton - emerging interrelations

Anke Zieseniss. Hypoxia (Auckl). .

Abstract

Recent progress in understanding the influence of hypoxia on cell function has revealed new information about the interrelationship between the actin cytoskeleton and hypoxia; nevertheless, details remain cloudy. The dynamic regulation of the actin cytoskeleton during hypoxia is complex, varies in different cells and tissues, and also depends on the mode of hypoxia. Several molecular players and pathways are emerging that contribute to the modulation of the actin cytoskeleton and that affect the large repertoire of actin-binding proteins in hypoxia. This review describes and discusses the accumulated knowledge about actin cytoskeleton dynamics in hypoxia, placing special emphasis on the Rho family of small guanosine triphosphatases (Rho GTPases). Given that RhoA, Rac and Cdc42 are very well characterized, the review is focused on these family members of Rho GTPases. Notably, in several cell types and tissues, hypoxia, presumably via Rho GTPase signaling, induces actin rearrangement and actin stress fiber assembly, which is a prevalent modulation of the actin cytoskeleton in hypoxia.

Keywords: Rho GTPases; RhoA; actin dynamics; stress fibers.

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Figures

Figure 1
Figure 1
The schema depicts mechanisms that are involved in actin filament reorganization, including stress fiber polymerization and stress fiber contraction in hypoxia. Cytoskeletal actin dynamics are affected by different classes of plasma membrane receptors, among them G-protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). The plasma-membrane receptors modulate the activity of Rho guanosine triphosphatases (Rho GTPases) through Rho guanine nucleotide-exchange factors (GEFs), which then orchestrate changes to the actin cytoskeleton via a variety of downstream effectors. HIF target genes (eg, VEGF) bind to plasma-membrane receptors, which could provide a way of hypoxic regulation of the actin cytoskeleton. Abbreviations: ECM, extracellular matrix; VEGF, vascular endothelial growth factor; FAK, focal adhesion kinase; NOX, nicotinamide adenine dinucleotide phosphate oxidase; ROS, reactive oxygen species; ROCK, Rho-associated protein kinase; LIMK, LIM-domain kinase; MLCK, myosin light-chain kinase; MLCP, MLC phosphatase; PHD, prolyl hydroxylase domain; SF, stress fiber; MK, mitogen-activated protein kinase; HSP, heat-shock protein.
Figure 2
Figure 2
Schematic representation of epithelial cells and the actin cytoskeleton reorganization in response to hypoxia/hypoxia-inducible factor (HIF)-α stabilization. HIF-1 is a critical regulator of the extracellular matrix (ECM) and changes integrin signaling and focal adhesion-complex formation. Furthermore, hypoxia influences the expression and activity of several actin-binding proteins like vasodilator-stimulated phosphoprotein (VASP) and zonula occludens (ZO)-1. Abbreviation: FAK, focal adhesion kinase.
Figure 3
Figure 3
Immunofluorescence images of L929 fibroblasts cultured under normoxic (20% O2) and hypoxic conditions (1% O2). Notes: There was an increase of F-actin in hypoxia. The third image shows a close-up of the dashed box in the second image. Green, F-actin; red, vinculin; blue, deoxyribonucleic acid.
See this image and copyright information in PMC

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