RT Journal Article
SR Electronic
T1 Intraneuronal delivery of protein kinase C pseudosubstrate leads to growth cone collapse
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7158
OP 7167
DO 10.1523/JNEUROSCI.15-11-07158.1995
VO 15
IS 11
A1 L Theodore
A1 D Derossi
A1 G Chassaing
A1 B Llirbat
A1 M Kubes
A1 P Jordan
A1 H Chneiweiss
A1 P Godement
A1 A Prochiantz
YR 1995
UL http://www.jneurosci.org/content/15/11/7158.abstract
AB 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.