Arp2/3 is a negative regulator of growth cone translocation.
Arp2/3 is an actin binding complex that is enriched in the peripheral lamellipodia of fibroblasts, where it forms a network of short, branched actin filaments, generating the protrusive force that extends lamellipodia and drives fibroblast motility. Although it has been assumed that Arp2/3 would play a similar role in growth cones, our studies indicate that Arp2/3 is enriched in the central, not the peripheral, region of growth cones and that the growth cone periphery contains few branched actin filaments. Arp2/3 inhibition in fibroblasts severely disrupts actin organization and membrane protrusion. In contrast, Arp2/3 inhibition in growth cones minimally affects actin organization and does not inhibit lamellipodia protrusion or de novo filopodia formation. Surprisingly, Arp2/3 inhibition significantly enhances axon elongation and causes defects in growth cone guidance. These results indicate that Arp2/3 is a negative regulator of growth cone translocation.
Strasser
Geraldine A
GA
Biology Department, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Rahim
Nazimah Abdul
NA
VanderWaal
Kristyn E
KE
Gertler
Frank B
FB
Lanier
Lorene M
LM
D008841:Actin Cytoskeleton / Q000378:metabolism*; D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D025461:Feedback, Physiological / Q000235:genetics; D005333:Fetus; D049452:Green Fluorescent Proteins; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D008164:Luminescent Proteins; D046911:Macromolecular Substances; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009420:Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D011554:Pseudopodia / Q000378:metabolism / Q000648:ultrastructure
D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; C495927:Actr2 protein, mouse; C495929:Actr3 protein, mouse; D003598:Cytoskeletal Proteins; D008164:Luminescent Proteins; D046911:Macromolecular Substances; D049452:Green Fluorescent Proteins