Possible role of cortactin phosphorylation by protein kinase Cα in actin-bundle formation at growth cone.

BACKGROUND INFORMATION:Cortactin contributes to growth cone morphogenesis by forming with dynamin, ring-shaped complexes that mechanically bundle and stabilise F-actin. However, the regulatory mechanism of cortactin action is poorly understood. RESULTS:Immunofluorescence microscopy revealed that protein kinase C α colocalises with cortactin at growth cone filopodia in SH-SY5Y neuroblastoma cells. activation by phorbol 12-myristate 13-acetate causes cortactin phosphorylation, filopodial retraction and F-actin-bundle loss. Moreover, directly phosphorylates cortactin in vitro at S135/T145/S172, mitigating both cortactin's actin-binding and actin-crosslinking activity, whereas cellular expression of a phosphorylation-mimetic cortactin mutant hinders filopodial formation with a significant decrease of actin bundles. CONCLUSIONS:Our results indicate that cortactin phosphorylation might be implicated in the maintenance of growth cone.

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