Critical Role of Ena/VASP Proteins for Filopodia Formation in Neurons and in Function Downstream of netrin-1

Neuron. 2004 Apr 8;42(1):37-49. doi: 10.1016/s0896-6273(04)00108-4.

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

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Analysis of Variance
  • Animals
  • Antibodies / pharmacology
  • Blood Proteins / metabolism
  • Blotting, Western / methods
  • Caenorhabditis elegans Proteins*
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism
  • Cell Adhesion Molecules / physiology*
  • Cell Count
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Chickens
  • Colforsin / pharmacology
  • Cytochalasin D / metabolism
  • Cytoskeletal Proteins / metabolism
  • Dendrites / metabolism
  • Gene Expression Regulation / physiology
  • Green Fluorescent Proteins
  • Growth Cones / drug effects
  • Growth Cones / metabolism
  • Hippocampus / cytology
  • Humans
  • Immunohistochemistry / methods
  • Luminescent Proteins / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Microfilament Proteins
  • Microscopy, Electron / methods
  • Mitochondria / metabolism
  • Nerve Growth Factors / physiology*
  • Netrin-1
  • Neuroglia / cytology
  • Neuroglia / drug effects
  • Neuroglia / physiology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / physiology*
  • Phosphoproteins / physiology*
  • Phosphorylation
  • Precipitin Tests / methods
  • Protein Structure, Tertiary / genetics
  • Pseudopodia / drug effects
  • Pseudopodia / physiology*
  • Pseudopodia / ultrastructure
  • Time Factors
  • Transfection / methods
  • Tubulin / metabolism
  • Tumor Suppressor Proteins

Substances

  • Antibodies
  • Blood Proteins
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • Enah protein, mouse
  • Evl protein, mouse
  • Luminescent Proteins
  • Membrane Proteins
  • Microfilament Proteins
  • NTN1 protein, human
  • Nerve Growth Factors
  • Ntn1 protein, mouse
  • Phosphoproteins
  • Tubulin
  • Tumor Suppressor Proteins
  • UNC-40 protein, C elegans
  • vasodilator-stimulated phosphoprotein
  • radixin
  • Green Fluorescent Proteins
  • Netrin-1
  • Colforsin
  • Cytochalasin D