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J Neurosci
2008 Jun 04;2823:5879-90. doi: 10.1523/JNEUROSCI.5331-07.2008.
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A molecular clutch between the actin flow and N-cadherin adhesions drives growth cone migration.
Bard L
,
Boscher C
,
Lambert M
,
Mège RM
,
Choquet D
,
Thoumine O
.
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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 extension.
Bekirov,
Cadherin-8 and N-cadherin differentially regulate pre- and postsynaptic development of the hippocampal mossy fiber pathway.
2008, Pubmed
Bekirov,
Cadherin-8 and N-cadherin differentially regulate pre- and postsynaptic development of the hippocampal mossy fiber pathway.
2008,
Pubmed
Benson,
N-cadherin redistribution during synaptogenesis in hippocampal neurons.
1998,
Pubmed
Biederer,
SynCAM, a synaptic adhesion molecule that drives synapse assembly.
2002,
Pubmed
Boscher,
Cadherin-11 interacts with the FGF receptor and induces neurite outgrowth through associated downstream signalling.
2008,
Pubmed
Bozdagi,
Increasing numbers of synaptic puncta during late-phase LTP: N-cadherin is synthesized, recruited to synaptic sites, and required for potentiation.
2000,
Pubmed
Bradke,
Neuronal polarity: vectorial cytoplasmic flow precedes axon formation.
1997,
Pubmed
Breillat,
Characterization of SynCAM surface trafficking using a SynCAM derived ligand with high homophilic binding affinity.
2007,
Pubmed
Cavallaro,
N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signalling.
2001,
Pubmed
Chen,
p120 catenin associates with kinesin and facilitates the transport of cadherin-catenin complexes to intercellular junctions.
2003,
Pubmed
Chu,
Force measurements in E-cadherin-mediated cell doublets reveal rapid adhesion strengthened by actin cytoskeleton remodeling through Rac and Cdc42.
2004,
Pubmed
Davis,
A core function for p120-catenin in cadherin turnover.
2003,
Pubmed
Dequidt,
Fast turnover of L1 adhesions in neuronal growth cones involving both surface diffusion and exo/endocytosis of L1 molecules.
2007,
Pubmed
Diefenbach,
Myosin 1c and myosin IIB serve opposing roles in lamellipodial dynamics of the neuronal growth cone.
2002,
Pubmed
Drees,
Alpha-catenin is a molecular switch that binds E-cadherin-beta-catenin and regulates actin-filament assembly.
2005,
Pubmed
Elia,
p120 catenin regulates dendritic spine and synapse development through Rho-family GTPases and cadherins.
2006,
Pubmed
El Sayegh,
Cortactin associates with N-cadherin adhesions and mediates intercellular adhesion strengthening in fibroblasts.
2004,
Pubmed
Eugène,
GABA(A) receptor gamma 2 subunit mutations linked to human epileptic syndromes differentially affect phasic and tonic inhibition.
2007,
Pubmed
Fischer,
Rapid actin-based plasticity in dendritic spines.
1998,
Pubmed
Ganz,
Traction forces exerted through N-cadherin contacts.
2006,
Pubmed
Gil,
Ankyrin binding mediates L1CAM interactions with static components of the cytoskeleton and inhibits retrograde movement of L1CAM on the cell surface.
2003,
Pubmed
Jiang,
Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin.
2003,
Pubmed
Kadowaki,
N-cadherin mediates cortical organization in the mouse brain.
2007,
Pubmed
Kamiguchi,
The role of endocytic l1 trafficking in polarized adhesion and migration of nerve growth cones.
2001,
Pubmed
Kobielak,
Alpha-catenin: at the junction of intercellular adhesion and actin dynamics.
2004,
Pubmed
Kucik,
Preferential attachment of membrane glycoproteins to the cytoskeleton at the leading edge of lamella.
1991,
Pubmed
Kucik,
Weak dependence of mobility of membrane protein aggregates on aggregate size supports a viscous model of retardation of diffusion.
1999,
Pubmed
Lambert,
Nucleation and growth of cadherin adhesions.
2007,
Pubmed
Lambert,
Immobilized dimers of N-cadherin-Fc chimera mimic cadherin-mediated cell contact formation: contribution of both outside-in and inside-out signals.
2000,
Pubmed
Lambert,
Dynamics of ligand-induced, Rac1-dependent anchoring of cadherins to the actin cytoskeleton.
2002,
Pubmed
Lamoureux,
Mechanical tension can specify axonal fate in hippocampal neurons.
2002,
Pubmed
Lemmon,
Neurite growth on different substrates: permissive versus instructive influences and the role of adhesive strength.
1992,
Pubmed
Lilien,
The juxtamembrane domain of cadherin regulates integrin-mediated adhesion and neurite outgrowth.
1999,
Pubmed
Lin,
Myosin drives retrograde F-actin flow in neuronal growth cones.
1996,
Pubmed
Lin,
Growth cone advance is inversely proportional to retrograde F-actin flow.
1995,
Pubmed
Mallavarapu,
Regulated actin cytoskeleton assembly at filopodium tips controls their extension and retraction.
1999,
Pubmed
Marthiens,
A novel function for cadherin-11 in the regulation of motor axon elongation and fasciculation.
2005,
Pubmed
Matsunaga,
Guidance of optic nerve fibres by N-cadherin adhesion molecules.
1988,
Pubmed
Mège,
Regulation of cell-cell junctions by the cytoskeleton.
2006,
Pubmed
Mitchison,
Cytoskeletal dynamics and nerve growth.
1988,
Pubmed
Nishimura,
L1-dependent neuritogenesis involves ankyrinB that mediates L1-CAM coupling with retrograde actin flow.
2003,
Pubmed
Okamura,
Cadherin activity is required for activity-induced spine remodeling.
2004,
Pubmed
Ozawa,
The membrane-proximal region of the E-cadherin cytoplasmic domain prevents dimerization and negatively regulates adhesion activity.
1998,
Pubmed
Palecek,
Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness.
1997,
Pubmed
Perret,
Trans-bonded pairs of E-cadherin exhibit a remarkable hierarchy of mechanical strengths.
2004,
Pubmed
Pittet,
Fibrogenic fibroblasts increase intercellular adhesion strength by reinforcing individual OB-cadherin bonds.
2008,
Pubmed
Riehl,
Cadherin function is required for axon outgrowth in retinal ganglion cells in vivo.
1996,
Pubmed
,
Xenbase
Saffell,
Expression of a dominant negative FGF receptor inhibits axonal growth and FGF receptor phosphorylation stimulated by CAMs.
1997,
Pubmed
Saglietti,
Extracellular interactions between GluR2 and N-cadherin in spine regulation.
2007,
Pubmed
Suter,
An emerging link between cytoskeletal dynamics and cell adhesion molecules in growth cone guidance.
1998,
Pubmed
Suter,
The Ig superfamily cell adhesion molecule, apCAM, mediates growth cone steering by substrate-cytoskeletal coupling.
1998,
Pubmed
Thoumine,
Weak effect of membrane diffusion on the rate of receptor accumulation at adhesive contacts.
2005,
Pubmed
Thoumine,
Regulation of N-cadherin dynamics at neuronal contacts by ligand binding and cytoskeletal coupling.
2006,
Pubmed
Thoumine,
A probabilistic model for ligand-cytoskeleton transmembrane adhesion: predicting the behavior of microspheres on the surface of migrating cells.
2000,
Pubmed
Togashi,
Cadherin regulates dendritic spine morphogenesis.
2002,
Pubmed
Yamada,
Deconstructing the cadherin-catenin-actin complex.
2005,
Pubmed
Yap,
The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p120ctn.
1998,
Pubmed
,
Xenbase
Yu,
Beta-catenin is critical for dendritic morphogenesis.
2003,
Pubmed
