title: Mechanical coupling between transsynaptic N-cadherin adhesions and actin flow stabilizes dendritic spines.
abstract: The morphology of neuronal dendritic spines is a critical indicator of synaptic function. It is regulated by several factors, including the intracellular actin/myosin cytoskeleton and transcellular N-cadherin adhesions. To examine the mechanical relationship between these molecular components, we performed quantitative live-imaging experiments in primary hippocampal neurons. We found that actin turnover and structural motility were lower in dendritic spines than in immature filopodia and increased upon expression of a nonadhesive N-cadherin mutant, resulting in an inverse relationship between spine motility and actin enrichment. Furthermore, the pharmacological stimulation of myosin II induced the rearward motion of actin structures in spines, showing that myosin II exerts tension on the actin network. Strikingly, the formation of stable, spine-like structures enriched in actin was induced at contacts between dendritic filopodia and N-cadherin-coated beads or micropatterns. Finally, computer simulations of actin dynamics mimicked various experimental conditions, pointing to the actin flow rate as an important parameter controlling actin enrichment in dendritic spines. Together these data demonstrate that a clutch-like mechanism between N-cadherin adhesions and the actin flow underlies the stabilization of dendritic filopodia into mature spines, a mechanism that may have important implications in synapse initiation, maturation, and plasticity in the developing brain.
authors.affiliation: Interdisciplinary Institute for Neuroscience, University of Bordeaux, Unité Mixte de Recherche 5297, F-33000 Bordeaux, France Interdisciplinary Institute for Neuroscience, Centre Nationale de la Recherche Scientifique, Unité Mixte de Recherche 5297, F-33000 Bordeaux, France.
authors.forename: Anaël
authors.initials: A
authors.lastname: Chazeau
authors.affiliation: Interdisciplinary Institute for Neuroscience, University of Bordeaux, Unité Mixte de Recherche 5297, F-33000 Bordeaux, France Interdisciplinary Institute for Neuroscience, Centre Nationale de la Recherche Scientifique, Unité Mixte de Recherche 5297, F-33000 Bordeaux, France CYTOO, Minatec, Grenoble, 38054 Grenoble, France.
authors.forename: Mikael
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Interdisciplinary Institute for Neuroscience, University of Bordeaux, Unité Mixte de Recherche 5297, F-33000 Bordeaux, France Interdisciplinary Institute for Neuroscience, Centre Nationale de la Recherche Scientifique, Unité Mixte de Recherche 5297, F-33000 Bordeaux, France.
authors.forename: Katalin
authors.initials: K
authors.lastname: Czöndör
authors.affiliation: Interdisciplinary Institute for Neuroscience, University of Bordeaux, Unité Mixte de Recherche 5297, F-33000 Bordeaux, France Interdisciplinary Institute for Neuroscience, Centre Nationale de la Recherche Scientifique, Unité Mixte de Recherche 5297, F-33000 Bordeaux, France.
authors.forename: David
authors.initials: D
authors.lastname: Perrais
authors.affiliation: Interdisciplinary Institute for Neuroscience, University of Bordeaux, Unité Mixte de Recherche 5297, F-33000 Bordeaux, France Interdisciplinary Institute for Neuroscience, Centre Nationale de la Recherche Scientifique, Unité Mixte de Recherche 5297, F-33000 Bordeaux, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Tessier
authors.affiliation: Interdisciplinary Institute for Neuroscience, University of Bordeaux, Unité Mixte de Recherche 5297, F-33000 Bordeaux, France Interdisciplinary Institute for Neuroscience, Centre Nationale de la Recherche Scientifique, Unité Mixte de Recherche 5297, F-33000 Bordeaux, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Giannone
authors.affiliation: Interdisciplinary Institute for Neuroscience, University of Bordeaux, Unité Mixte de Recherche 5297, F-33000 Bordeaux, France Interdisciplinary Institute for Neuroscience, Centre Nationale de la Recherche Scientifique, Unité Mixte de Recherche 5297, F-33000 Bordeaux, France olivier.thoumine@u-bordeaux.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Thoumine
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology; D024462:Myosin Type II / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D013569:Synapses / Q000502:physiology*
chemical_list: D000199:Actins; D015820:Cadherins; D024462:Myosin Type II