Protein kinase C-δ C2-like domain is a binding site for actin and enables actin redistribution in neutrophils

Neutrophils play a key role in host-defence mechanisms against invading pathogens, using their capacity to migrate, engulf micro-organisms and produce toxic radicals. Protein kinase C (PKC) isotypes are important intracellular regulators of these processes in neutrophils. PKC isotypes themselves are controlled by interactions with lipids. Ca2+ and proteins. The C2-like domain of PKC-delta (delta C2) has been identified as a protein-interaction domain in this PKC isotype. In the present paper we have investigated the contribution of protein interactions at this domain to the regulation/function of PKC-delta in neutrophils. Using affinity chromatography we identified actin as a delta C2 binding partner in these cells. Fluorescein-labelled delta C2, micro- injected into immobilized neutrophils, interacts with filamentous actin (F-actin) inside the cell. PKC-delta co-localizes with F-actin in neutrophils, in lamellipodia at the leading edge of the cell. Stimulation with phorbol ester or IgG-opsonized Staphylococcus ureus results in co-ordinated redistribution of PKC-delta and F-actin, and a PKC-delta inhibitor inhibits these changes. Microinjection of delta C2 also inhibits F-actin redistribution. Thus PKC-delta binds to F-actin through its C2 domain, and these interactions are important in regulating actin redistribution in neutrophils.