cortactin is involved in the entry of coxiella burnetii into non-phagocytic cellscortactin参与伯纳特氏立克次氏体进入non-phagocytic细胞.pdfVIP

Cortactin Is Involved in the Entry of Coxiella burnetii into Non-Phagocytic Cells 1 1 1 1 ´ 1 Eliana M. Rosales , Milton O. Aguilera , Romina P. Salinas , Sergio A. Carminati , Marıa I. Colombo , 2 ´ 1 Narcisa Martinez-Quiles , Walter Beron * ´ ´ ´ ´ 1 Instituto de Histologıa y Embriologıa, Facultad de Ciencias Medicas, Universidad Nacional de Cuyo - CONICET, Mendoza, Argentina, 2 Microbiologıa II, Facultad de ˜ Farmacia, Universidad Complutense de Madrid, Madrid, Espana Abstract Background: Cortactin is a key regulator of the actin cytoskeleton and is involved in pathogen-host cell interactions. Numerous pathogens exploit the phagocytic process and actin cytoskeleton to infect host cells. Coxiella burnetii, the etiologic agent of Q fever, is internalized by host cells through a molecular mechanism that is poorly understood. Methodology/Principal Finding: Here we analyzed the role of different cortactin motifs in the internalization of C. burnetii by non-phagocytic cells. C. burnetii internalization into HeLa cells was significantly reduced when the cells expressed GFP- cortactin W525K, which carries a mutation in the SH3 domain that renders the protein unable to bind targets such as N- WASP. However, internalization was unaffected when the cells expressed the W22A mutant, which has a mutation in the N- terminal acidic region that destroys the protein’s ability to bind and activate Arp2/3. We also determin