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Intraneuronal delivery of protein kinase C pseudosubstrate leads to growth cone collapse

L Theodore, D Derossi, G Chassaing, B Llirbat, M Kubes, P Jordan, H Chneiweiss, P Godement and A Prochiantz
Journal of Neuroscience 1 November 1995, 15 (11) 7158-7167; DOI: https://doi.org/10.1523/JNEUROSCI.15-11-07158.1995
L Theodore
URA 1414, Centre National de la Recherche Scientifique, Ecole Normale Superieure, Paris, France.
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D Derossi
URA 1414, Centre National de la Recherche Scientifique, Ecole Normale Superieure, Paris, France.
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G Chassaing
URA 1414, Centre National de la Recherche Scientifique, Ecole Normale Superieure, Paris, France.
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B Llirbat
URA 1414, Centre National de la Recherche Scientifique, Ecole Normale Superieure, Paris, France.
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M Kubes
URA 1414, Centre National de la Recherche Scientifique, Ecole Normale Superieure, Paris, France.
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P Jordan
URA 1414, Centre National de la Recherche Scientifique, Ecole Normale Superieure, Paris, France.
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H Chneiweiss
URA 1414, Centre National de la Recherche Scientifique, Ecole Normale Superieure, Paris, France.
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P Godement
URA 1414, Centre National de la Recherche Scientifique, Ecole Normale Superieure, Paris, France.
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A Prochiantz
URA 1414, Centre National de la Recherche Scientifique, Ecole Normale Superieure, Paris, France.
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Abstract

Axonal navigation during development requires that cues present in the extracellular environment be capable of modifying the structure of the cone in a dynamic way. Protein kinase C (PKC) has long been suspected to be one of the multiple molecular relays present in the terminal structure of the developing axon and involved in the transduction of extracellular signals. The latter proposal is, however, based on the use of drugs or of protocols leading to pleiotropic and often nonspecific effects. In the present study, we have taken advantage of the discovery of a peptide capable of translocating across biological membranes and to accumulate in the cytoplasm and nucleus of cells in culture, to internalize a highly specific peptidic inhibitor of PKC. We demonstrate that linking the two peptides (vector and PKC inhibitor) allows the internalization of the latter in live cells, specifically inhibits PKC and provokes a rapid modification of growth cone morphology. This set of data thus establishes that a peptidic inhibitor of PKC activity, once internalized, provokes a change in growth cone morphology, reminiscent of the collapse phenotype. In addition, the present study describes a new efficient and harmless way to introduce pharmacologically active substances in neural cells in culture.

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The Journal of Neuroscience: 15 (11)
Journal of Neuroscience
Vol. 15, Issue 11
1 Nov 1995
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Intraneuronal delivery of protein kinase C pseudosubstrate leads to growth cone collapse
L Theodore, D Derossi, G Chassaing, B Llirbat, M Kubes, P Jordan, H Chneiweiss, P Godement, A Prochiantz
Journal of Neuroscience 1 November 1995, 15 (11) 7158-7167; DOI: 10.1523/JNEUROSCI.15-11-07158.1995

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Intraneuronal delivery of protein kinase C pseudosubstrate leads to growth cone collapse
L Theodore, D Derossi, G Chassaing, B Llirbat, M Kubes, P Jordan, H Chneiweiss, P Godement, A Prochiantz
Journal of Neuroscience 1 November 1995, 15 (11) 7158-7167; DOI: 10.1523/JNEUROSCI.15-11-07158.1995
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