Abstract
Growth cones contain mRNAs, translation machinery, and, as we report here, protein degradation machinery. We show that isolated retinal growth cones immediately lose their ability to turn in a chemotropic gradient of netrin-1 or Sema3A when translation is inhibited. Translation inhibition also prevents Sema3A-induced collapse, while LPA-induced collapse is not affected. Inhibition of proteasome function blocks responses to netrin-1 and LPA but does not affect Sema3A responses. We further demonstrate in isolated growth cones that netrin-1 and Sema3A activate translation initiation factors and stimulate a marked rise in protein synthesis within minutes, while netrin-1 and LPA elicit similar rises in ubiquitin-protein conjugates. These results suggest that guidance molecules steer axon growth by triggering rapid local changes in protein levels in growth cones.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amanitins / pharmacology
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Animals
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Carrier Proteins / metabolism
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Cysteine Endopeptidases / metabolism
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Cysteine Proteinase Inhibitors / pharmacology
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Drosophila Proteins*
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Eukaryotic Initiation Factor-4E
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Eye Proteins / genetics*
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Eye Proteins / metabolism*
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Glycoproteins / pharmacology
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Growth Cones / physiology*
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Leupeptins / pharmacology
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Lipopolysaccharides / pharmacology
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Multienzyme Complexes / antagonists & inhibitors
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Multienzyme Complexes / metabolism
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Nerve Growth Factors / pharmacology
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Netrin-1
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Nucleic Acid Synthesis Inhibitors / pharmacology
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Peptide Initiation Factors / metabolism
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoproteins / metabolism
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Proteasome Endopeptidase Complex
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Protein Biosynthesis / drug effects
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Protein Biosynthesis / physiology*
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Receptor Protein-Tyrosine Kinases / metabolism
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Retina / cytology*
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Retina / growth & development
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Semaphorin-3A
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Tumor Suppressor Proteins
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Ubiquitin / metabolism
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Xenopus
Substances
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Amanitins
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Carrier Proteins
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Cysteine Proteinase Inhibitors
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Drosophila Proteins
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Eukaryotic Initiation Factor-4E
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Eye Proteins
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Glycoproteins
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Leupeptins
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Lipopolysaccharides
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Multienzyme Complexes
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Nerve Growth Factors
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Nucleic Acid Synthesis Inhibitors
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Peptide Initiation Factors
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Phosphoproteins
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Semaphorin-3A
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Tumor Suppressor Proteins
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Ubiquitin
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acetylleucyl-leucyl-norleucinal
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Netrin-1
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Phosphatidylinositol 3-Kinases
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Receptor Protein-Tyrosine Kinases
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tor protein, Drosophila
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex