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Sci. Signal., 7 February 2012
Vol. 5, Issue 210, p. ra12
[DOI: 10.1126/scisignal.2002448]

RESEARCH ARTICLES

PTEN Directly Activates the Actin Depolymerization Factor Cofilin-1 During PGE2-Mediated Inhibition of Phagocytosis of Fungi

C. Henrique Serezani1, Steve Kane1, Alexandra I. Medeiros2, Ashley M. Cornett1, Sang-Hoon Kim3, Mariana Morato Marques4, Sang-Pyo Lee5, Casey Lewis1, Emilie Bourdonnay1, Megan N. Ballinger1, Eric S. White1, and Marc Peters-Golden1*

1 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI 48109, USA.
2 Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University–UNESP, Araraquara 14801-902, Brazil.
3 Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Eulji University School of Medicine, Seoul 139-711, South Korea.
4 Department of Immunology, Institute of Biomedical Science IV, University of São Paulo, São Paulo 05508-000, Brazil.
5 Division of Allergy, Gachon University Gil Hospital, Incheon 405-760, South Korea.

Abstract: 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 E2 (PGE2) and generation of cyclic adenosine monophosphate (cAMP) also accompany this process. Here, we characterized the mechanisms underlying PGE2-mediated inhibition of phagocytosis and filamentous actin (F-actin) polymerization in response to ingestion of C. albicans by alveolar macrophages. PGE2 suppressed phagocytosis and F-actin formation through the PGE2 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 PGE2. PGE2-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 PGE2 accompanies many immunosuppressed states, the PTEN-dependent pathway described here may contribute to impaired antifungal defenses.

* To whom correspondence should be addressed. E-mail: petersm{at}umich.edu

Citation: C. H. Serezani, S. Kane, A. I. Medeiros, A. M. Cornett, S.-H. Kim, M. M. Marques, S.-P. Lee, C. Lewis, E. Bourdonnay, M. N. Ballinger, E. S. White, M. Peters-Golden, PTEN Directly Activates the Actin Depolymerization Factor Cofilin-1 During PGE2-Mediated Inhibition of Phagocytosis of Fungi. Sci. Signal. 5, ra12 (2012).

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