Abstract
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.
Publication types
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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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Actin-Related Protein 2
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Actin-Related Protein 3
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Amino Acid Sequence / genetics
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Animals
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Animals, Newborn
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Cell Differentiation / genetics
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Cell Movement / genetics*
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Cells, Cultured
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / physiology*
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Feedback, Physiological / genetics
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Fetus
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Green Fluorescent Proteins
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Growth Cones / metabolism*
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Growth Cones / ultrastructure
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Luminescent Proteins
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Macromolecular Substances
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Mice
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Microtubules / metabolism
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Nervous System / cytology
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Nervous System / embryology*
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Nervous System / metabolism
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Protein Binding / genetics
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Protein Structure, Tertiary / genetics
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Pseudopodia / metabolism
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Pseudopodia / ultrastructure
Substances
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Actin-Related Protein 2
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Actin-Related Protein 3
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Actr2 protein, mouse
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Actr3 protein, mouse
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Cytoskeletal Proteins
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Luminescent Proteins
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Macromolecular Substances
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Green Fluorescent Proteins