Netrin-1 Attracts axons through FAK-dependent mechanotransduction

Simon W. Moore Dr., Xian Zhang, Christopher D. Lynch, Michael Sheetz

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The mechanism by which extracellular cues influence intracellular biochemical cascades that guide axons is important, yet poorly understood. Because of the mechanical nature of axon extension, we explored whether the physical interactions of growth cones with their guidance cues might be involved. In the context of mouse spinal commissural neuron axon attraction to netrin-1, we found that mechanical attachment of netrin-1 to the substrate was required for axon outgrowth, growth cone expansion, axon attraction and phosphorylation of focal adhesion kinase (FAK) and Crk-associated substrate (CAS). Myosin II activity was necessary for traction forces >30 pN on netrin-1. Interestingly, while these myosin II-dependent forces on netrin-1 substrates or beads were needed to increase the kinase activity and phosphorylation of FAK, they were not necessary for netrin-1 to increase CAS phosphorylation. When FAK kinase activity was inhibited, the growth cone's ability to recruit additional adhesions and to generate forces >60 pN on netrin-1 was disrupted. Together, these findings demonstrate an important role for mechanotransduction during chemoattraction to netrin-1 and that mechanical activation of FAK reinforces interactions with netrin-1 allowing greater forces to be exerted.

Original languageEnglish (US)
Pages (from-to)11574-11585
Number of pages12
JournalJournal of Neuroscience
Volume32
Issue number34
DOIs
StatePublished - Aug 22 2012
Externally publishedYes

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Focal Adhesion Protein-Tyrosine Kinases
Axons
Growth Cones
Crk-Associated Substrate Protein
Myosin Type II
Phosphorylation
Cues
Phosphotransferases
Aptitude
netrin-1
Traction
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Netrin-1 Attracts axons through FAK-dependent mechanotransduction. / Moore Dr., Simon W.; Zhang, Xian; Lynch, Christopher D.; Sheetz, Michael.

In: Journal of Neuroscience, Vol. 32, No. 34, 22.08.2012, p. 11574-11585.

Research output: Contribution to journalArticle

Moore Dr., Simon W. ; Zhang, Xian ; Lynch, Christopher D. ; Sheetz, Michael. / Netrin-1 Attracts axons through FAK-dependent mechanotransduction. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 34. pp. 11574-11585.
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