Otro
PTEN Directly Activates the Actin Depolymerization Factor Cofilin-1 During PGE(2)-Mediated Inhibition of Phagocytosis of Fungi
Registro en:
Science Signaling. Washington: Amer Assoc Advancement Science, v. 5, n. 210, p. 10, 2012.
1937-9145
10.1126/scisignal.2002448
WOS:000300610300002
Autor
Serezani, C. Henrique
Kane, Steve
Medeiros, Alexandra Ivo de
Cornett, Ashley M.
Kim, Sang-Hoon
Marques, Mariana Morato
Lee, Sang-Pyo
Lewis, Casey
Bourdonnay, Emilie
Ballinger, Megan N.
White, Eric S.
Peters-Golden, Marc
Resumen
Macrophage ingestion of the yeast Candida albicans requires its recognition by multiple receptors and the activation of diverse signaling programs. Synthesis of the lipid mediator prostaglandin E-2 (PGE(2)) and generation of cyclic adenosine monophosphate (cAMP) also accompany this process. Here, we characterized the mechanisms underlying PGE(2)-mediated inhibition of phagocytosis and filamentous actin (F-actin) polymerization in response to ingestion of C. albicans by alveolar macrophages. PGE(2) suppressed phagocytosis and F-actin formation through the PGE(2) receptors EP2 and EP4, cAMP, and activation of types I and II protein kinase A. Dephosphorylation and activation of the actin depolymerizing factor cofilin-1 were necessary for these inhibitory effects of PGE(2). PGE(2)-dependent activation of cofilin-1 was mediated by the protein phosphatase activity of PTEN (phosphatase and tensin homolog deleted on chromosome 10), with which it directly associated. Because enhanced production of PGE(2) accompanies many immunosuppressed states, the PTEN-dependent pathway described here may contribute to impaired antifungal defenses. Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)