Critical role of Ena/VASP proteins for filopodia formation in neurons and in function downstream of netrin-1.
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.
Lebrand
Cecile
C
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Dent
Erik W
EW
Strasser
Geraldine A
GA
Lanier
Lorene M
LM
Krause
Matthias
M
Svitkina
Tatyana M
TM
Borisy
Gary G
GG
Gertler
Frank B
FB
D008841:Actin Cytoskeleton / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D002452:Cell Count; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002645:Chickens; D005576:Colforsin / Q000494:pharmacology; D015638:Cytochalasin D / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D049452:Green Fluorescent Proteins; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008164:Luminescent Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins; D008854:Microscopy, Electron / Q000379:methods; D008928:Mitochondria / Q000378:metabolism; D009414:Nerve Growth Factors / Q000502:physiology*; D000075388:Netrin-1; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D011233:Precipitin Tests / Q000379:methods; D017434:Protein Structure, Tertiary / Q000235:genetics; D011554:Pseudopodia / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014404:Tubulin / Q000378:metabolism; D025521:Tumor Suppressor Proteins; D000098662:Vasodilator-Stimulated Phosphoprotein
D000906:Antibodies; D001798:Blood Proteins; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C102176:Enah protein, mouse; C102177:Evl protein, mouse; D008164:Luminescent Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D010750:Phosphoproteins; D014404:Tubulin; D025521:Tumor Suppressor Proteins; C102174:UNC-40 protein, C elegans; D000098662:Vasodilator-Stimulated Phosphoprotein; C071776:radixin; D049452:Green Fluorescent Proteins; D000075388:Netrin-1; D005576:Colforsin; D015638:Cytochalasin D