THE INTERNALIZATION OF COXIELLA BURNETII BY THE HOST CELL IS REGULATED BY CORTACTIN.

ROSALES, E; AGUILERA, M; SALINAS, R; CARMINATI, S; BERÓN, W

Villa Carlos Paz, Córdoba

Congreso; XLIV Reunión Anual Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular; 2008

Sociedad Argentina de Investigaciones en Bioquímicas y Biología Molecular

Cortactin is a protein involved in the actin cytoskeleton organization regulating ruffles and lamellipodia formation during cell migration. In those processes cortactin is recruited to membrane in a PI3K-Rac1 dependent manner. Cortactin has different domains to interact with actin, and actin efectors such as Arp2/3 and N-WASP. The interaction is regulated by Tyr and Ser phosphorylation catalyzed by Src and Erk kinases, respectively. It has been shown that cortactin plays role in host cell-pathogen interaction. Adhesion, invasion or actin-based motility of pathogens such as E.coli, Chlamydia, Shigella and Listeria are regulated by cortactin. Coxiella burnetii (Cb) is an obligated intracellular pathogen that after phagocytosed form a parasitophorous vacuole in the host cell. We previously observed that cortactin regulates the Cb phagocytosis. To study if PI3K and Src proteins are involved in the internalization of Cb, HeLa cells were treated with wortmanin (Wn) or PP2, inhibitors of PI3K and Src, respectively, before infection. The adhered and intenalized bacteria were estimated by indirect immunofluorescence and confocal microscopy. We observed that Wn did not affect adhesion but inhibited internalization, while PP2 stimulated adhesion and internalization. These results suggest that PI3K and Src are involved in the interaction of Cb with host cell likely through cortactin.