Abstract
Ena/VASP proteins play important roles in axon outgrowth and guidance. Ena/VASP activity regulates the assembly and geometry of actin networks within fibroblast lamellipodia. In growth cones, Ena/VASP proteins are concentrated at filopodia tips, yet their role in growth cone responses to guidance signals has not been established. We found that Ena/VASP proteins play a pivotal role in formation and elongation of filopodia along neurite shafts and growth cone. Netrin-1-induced filopodia formation was dependent upon Ena/VASP function and directly correlated with Ena/VASP phosphorylation at a regulatory PKA site. Accordingly, Ena/VASP function was required for filopodial formation from the growth cone in response to global PKA activation. We propose that Ena/VASP proteins control filopodial dynamics in neurons by remodeling the actin network in response to guidance cues.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actin Cytoskeleton / metabolism
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Analysis of Variance
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Animals
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Antibodies / pharmacology
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Blood Proteins / metabolism
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Blotting, Western / methods
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Caenorhabditis elegans Proteins*
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Carrier Proteins / metabolism
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Carrier Proteins / physiology*
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Cell Adhesion Molecules / immunology
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Cell Adhesion Molecules / metabolism
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Cell Adhesion Molecules / physiology*
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Cell Count
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Cells, Cultured
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Cerebral Cortex / cytology
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Chickens
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Colforsin / pharmacology
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Cytochalasin D / metabolism
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Cytoskeletal Proteins / metabolism
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Dendrites / metabolism
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Gene Expression Regulation / physiology
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Green Fluorescent Proteins
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Growth Cones / drug effects
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Growth Cones / metabolism
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Hippocampus / cytology
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Humans
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Immunohistochemistry / methods
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Luminescent Proteins / metabolism
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Membrane Proteins / metabolism
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Mice
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Microfilament Proteins
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Microscopy, Electron / methods
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Mitochondria / metabolism
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Nerve Growth Factors / physiology*
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Netrin-1
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Neuroglia / cytology
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Neuroglia / drug effects
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Neuroglia / physiology
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Neurons / cytology
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Neurons / drug effects
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Neurons / physiology*
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Phosphoproteins / physiology*
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Phosphorylation
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Precipitin Tests / methods
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Protein Structure, Tertiary / genetics
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Pseudopodia / drug effects
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Pseudopodia / physiology*
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Pseudopodia / ultrastructure
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Time Factors
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Transfection / methods
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Tubulin / metabolism
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Tumor Suppressor Proteins
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Vasodilator-Stimulated Phosphoprotein
Substances
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Antibodies
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Blood Proteins
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Caenorhabditis elegans Proteins
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Carrier Proteins
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Cell Adhesion Molecules
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Cytoskeletal Proteins
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Enah protein, mouse
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Evl protein, mouse
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Luminescent Proteins
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Membrane Proteins
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Microfilament Proteins
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NTN1 protein, human
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Nerve Growth Factors
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Ntn1 protein, mouse
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Phosphoproteins
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Tubulin
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Tumor Suppressor Proteins
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UNC-40 protein, C elegans
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Vasodilator-Stimulated Phosphoprotein
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radixin
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Green Fluorescent Proteins
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Netrin-1
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Colforsin
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Cytochalasin D