Clutching at guidance cues: the integrin–FAK axis steers axon outgrowth
Clutching at guidance cues: the integrin–FAK axis steers axon outgrowth
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.
adhesion complex, axon regeneration, extracellular matirx, focal adhesion kinase, growth cone, integrin, kindlin, neurite outgrowth, point contact, talin, extracellular matrix
Davis-Lunn, Mathew James
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Goult, Benjamin T.
c2d6ef73-2c3f-4335-93f3-7327caddd6cb
Andrews, Melissa
ae987a2f-878e-4ae3-a7a3-a7170712096c
3 July 2023
Davis-Lunn, Mathew James
e249dade-ecc2-43d8-ae17-4663e67f3f2f
Goult, Benjamin T.
c2d6ef73-2c3f-4335-93f3-7327caddd6cb
Andrews, Melissa
ae987a2f-878e-4ae3-a7a3-a7170712096c
Davis-Lunn, Mathew James, Goult, Benjamin T. and Andrews, Melissa
(2023)
Clutching at guidance cues: the integrin–FAK axis steers axon outgrowth.
Biology, 12 (7), [954].
(doi: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.
Text
biology-12-00954-v2
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More information
Accepted/In Press date: 30 June 2023
e-pub ahead of print date: 3 July 2023
Published date: 3 July 2023
Additional Information:
Funding Information:
M.D.-L. is supported by a studentship funded by the Biotechnology and Biological Sciences Research Council (BBSRC) (Reference number: 2596704).
Publisher Copyright:
© 2023 by the authors.
Keywords:
adhesion complex, axon regeneration, extracellular matirx, focal adhesion kinase, growth cone, integrin, kindlin, neurite outgrowth, point contact, talin, extracellular matrix
Identifiers
Local EPrints ID: 479412
URI: http://eprints.soton.ac.uk/id/eprint/479412
ISSN: 2079-7737
PURE UUID: 46e4c12a-5fd5-4fa4-a0e1-4312d38455b1
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Date deposited: 21 Jul 2023 16:51
Last modified: 06 Jun 2024 02:09
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Author:
Benjamin T. Goult
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