Protein kinase C alpha (PKCalpha) participates in F-actin remodeling during phagocytosis and phagosomal maturation in macrophages. Leishmania donovani promastigotes, which inhibit phagosomal maturation, cause accumulation of periphagosomal F-actin instead of the dissassembly observed around other prey [Cell. Microbiol. 7 (2001) 439]. This accumulation is induced by promastigote lipophosphoglycan (LPG), which has several effects on macrophages including inhibition of PKCalpha. To investigate a possible connection between PKCot and LPG's effects on actin dynamics, we utilized RAW264.7 macrophages overexpressing dominant-negative PKCalpha (DN PKCalpha). We found increased cortical F-actin and decreased phagocytic capacity, as well as defective periphagosomal F-actin breakdown and inhibited phagosomal maturation in the DN PKCalpha-overexpressing cells, effects similar to those seen in controls subjected to LPG-coated prey. The results indicate that PKCalpha is involved in F-actin turnover in macrophages and that PKCalpha-dependent breakdown of periphagosomal F-actin is required for phagosomal maturation, and endorse the hypothesis that intracellular survival of L. donovani involves inhibition of PKCalpha by LPG. (C) 2003 Elsevier Science (USA). All rights reserved.