A molecular clutch between the actin flow and N-cadherin adhesions drives growth cone migration

L. Bard, C. Boscher, M. Lambert, R.-M. Mege, D. Choquet, O. Thoumine
Journal of Neuroscience. 2008-06-04; 28(23): 5879-5890
DOI: 10.1523/JNEUROSCI.5331-07.2008

Lire sur PubMed

1. J Neurosci. 2008 Jun 4;28(23):5879-90. doi: 10.1523/JNEUROSCI.5331-07.2008.

A molecular clutch between the actin flow and N-cadherin adhesions drives growth
cone migration.

Bard L(1), Boscher C, Lambert M, Mège RM, Choquet D, Thoumine O.

Author information:
(1)Unité Mixte de Recherche 5091, Centre National de la Recherche Scientifique,
Institut Francois Magendie, Université Bordeaux 2, 33077 Bordeaux, France.

The adhesion molecule N-cadherin plays important roles in the development of the
nervous system, in particular by stimulating axon outgrowth, but the molecular
mechanisms underlying this effect are mostly unknown. One possibility, the
so-called « molecular clutch » model, could involve a direct mechanical linkage
between N-cadherin adhesion at the membrane and intracellular actin-based
motility within neuronal growth cones. Using live imaging of primary rat
hippocampal neurons plated on N-cadherin-coated substrates and optical trapping
of N-cadherin-coated microspheres, we demonstrate here a strong correlation
between growth cone velocity and the mechanical coupling between ligand-bound
N-cadherin receptors and the retrograde actin flow. This relationship holds by
varying ligand density and expressing mutated N-cadherin receptors or small
interfering RNAs to perturb binding to catenins. By restraining microsphere
motion using optical tweezers or a microneedle, we further show slippage of
cadherin-cytoskeleton bonds at low forces, and, at higher forces, local actin
accumulation, which strengthens nascent N-cadherin contacts. Together, these data
support a direct transmission of actin-based traction forces to N-cadherin
adhesions, through catenin partners, driving growth cone advance and neurite

DOI: 10.1523/JNEUROSCI.5331-07.2008
PMCID: PMC6670336
PMID: 18524892 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus