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Review
. 2018 Mar 10;7(3):20.
doi: 10.3390/cells7030020.

Integrin Activation: Implications for Axon Regeneration

Menghon Cheah  1   2 , Melissa R Andrews  3
Affiliations
Review

Integrin Activation: Implications for Axon Regeneration

Menghon Cheah et al. Cells. .

Abstract

Integrin activation is essential for creating functional transmembrane receptors capable of inducing downstream cellular effects such as cell migration, cell spreading, neurite outgrowth and axon regeneration. Integrins are bidirectional signalling molecules that mediate their effects by 'inside-out' and 'outside-in' signalling. This review will provide a detailed overview of integrin activation focusing on intracellular activation in neurons and discussing direct implications in the regulation of neurite outgrowth and axon regeneration.

Keywords: extracellular matrix; gene therapy; integrin activation; kindlin; regeneration; talin; tenascin.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Integrin Structure and Activation. Activation of integrin heterodimers leads to intracellular signalling cascades and resulting processes such as cell motility, cell survival, cell differentiation, cell differentiation and neurite outgrowth. Schematic representing integrin conformations at the membrane including changes that occur with ‘Inside–Out signalling’ and ‘Outside–In signalling’. An inactivated integrin heterodimer exists with a closed and bent conformation (extracellularly) stabilised by a cytoplasmic salt bridge. This conformation has a very low ligand binding affinity. With Inside–Out signalling, intracellular activators (such as kindlin and talin) bind the β subunit cytoplasmically and interact/destabilise the salt bridge, leading to an open and extended (active) conformation with increased ligand binding affinity. With Outside–In signalling, binding of a ligand (ECM molecules such as laminin, fibronectin, or tenascin) extracellularly occurs as a result of integrin activation leading to a conformational change to an open and extended (active) conformation with high ligand binding affinity. Individual names of the extracellular domain components have been shown in the Outside–In signalling example for simplicity, with further explanation in the main text.
Figure 2
Figure 2
Focal adhesion formation. Schematic representing integrin receptor clustering at the membrane as an example of receptor activation, a result of ligand (ECM) binding and one of the resulting changes following ’outside–in’ signalling.
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