Clutching at Guidance Cues: The Integrin-FAK Axis Steers Axon Outgrowth.

Davis-Lunn, Mathew ORCID: 0000-0003-0677-9660, Goult, Benjamin T ORCID: 0000-0002-3438-2807 and Andrews, Melissa R ORCID: 0000-0001-5960-5619 (2023) Clutching at Guidance Cues: The Integrin-FAK Axis Steers Axon Outgrowth. Biology, 12 (7). 954-.

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Official URL: http://dx.doi.org/10.3390/biology12070954

Abstract

Integrin receptors are essential contributors to neurite outgrowth and axon elongation. Activated integrins engage components of the extracellular matrix, enabling the growth cone to form point contacts, which connect the extracellular substrate to dynamic intracellular protein complexes. These adhesion complexes facilitate efficient growth cone migration and neurite extension. Major signalling pathways mediated by the adhesion complex are instigated by focal adhesion kinase (FAK), whilst axonal guidance molecules present in vivo promote growth cone turning or retraction by local modulation of FAK activity. Activation of FAK is marked by phosphorylation following integrin engagement, and this activity is tightly regulated during neurite outgrowth. FAK inhibition slows neurite outgrowth by reducing point contact turnover; however, mutant FAK constructs with enhanced activity stimulate aberrant outgrowth. Importantly, FAK is a major structural component of maturing adhesion sites, which provide the platform for actin polymerisation to drive leading edge advance. In this review, we discuss the coordinated signalling of integrin receptors and FAK, as well as their role in regulating neurite outgrowth and axon elongation. We also discuss the importance of the integrin-FAK axis in vivo, as integrin expression and activation are key determinants of successful axon regeneration following injury.

Item Type:	Article
Uncontrolled Keywords:	adhesion complex, axon regeneration, extracellular matrix, focal adhesion kinase, growth cone, integrin, kindlin, neurite outgrowth, point contact, talin
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	04 Mar 2024 09:23
Last Modified:	04 Mar 2024 09:23
DOI:	10.3390/biology12070954
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179050