Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-2601
Amstutz, B; Gastaldelli, M; Kälin, S; Imelli, N; Boucke, K; Wandeler, E; Mercer, J; Hemmi, S; Greber, U F (2008). Subversion of CtBP1-controlled macropinocytosis by human adenovirus serotype 3. EMBO Journal, 27(7):956-969.
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Endocytosis supports cell communication, growth, and pathogen infection. The species B human adenovirus serotype 3 (Ad3) is associated with epidemic conjunctivitis, and fatal respiratory and systemic disease. Here we show that Ad3 uses dynamin-independent endocytosis for rapid infectious entry into epithelial and haematopoietic cells. Unlike Ad5, which uses dynamin-dependent endocytosis, Ad3 endocytosis spatially and temporally coincided with enhanced fluid-phase uptake. It was sensitive to macropinocytosis inhibitors targeting F-actin, protein kinase C, the sodium-proton exchanger, and Rac1 but not Cdc42. Infectious Ad3 macropinocytosis required viral activation of p21-activated kinase 1 (PAK1) and the C-terminal binding protein 1 of E1A (CtBP1), recruited to macropinosomes. These macropinosomes also contained the Ad3 receptors CD46 and alpha v integrins. CtBP1 is a phosphorylation target of PAK1, and is bifunctionally involved in membrane traffic and transcriptional repression of cell cycle, cancer, and innate immunity pathways. Phosphorylation-defective S147A-CtBP1 blocked Ad3 but not Ad5 infection, providing a direct link between PAK1 and CtBP1. The data show that viruses induce macropinocytosis for infectious entry, a pathway used in antigen presentation and cell migration.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||07 Faculty of Science > Institute of Molecular Life Sciences|
|DDC:||570 Life sciences; biology|
|Uncontrolled Keywords:||infectious disease / endocytosis / cell defense / transcription / innate immunity|
|Date:||06 March 2008|
|Deposited On:||18 Jun 2008 16:26|
|Last Modified:||28 Nov 2013 01:25|
|Publisher:||Nature Publishing Group|
|Citations:||Web of Science®. Times Cited: 80|
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