Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-729
Meier, O; Boucke, K; Hammer, S V; Keller, S; Stidwill, R P; Hemmi, S; Greber, U F (2002). Adenovirus triggers macropinocytosis and endosomal leakage together with its clathrin-mediated uptake. Journal of Cell Biology, 158(6):1119-1131.
View at publisher
Adenovirus type 2 (Ad2) binds the coxsackie B virus Ad receptor and is endocytosed upon activation of the alphav integrin coreceptors. Here, we demonstrate that expression of dominant negative clathrin hub, eps15, or K44A-dynamin (dyn) inhibited Ad2 uptake into epithelial cells, indicating clathrin-dependent viral endocytosis. Surprisingly, Ad strongly stimulated the endocytic uptake of fluid phase tracers, coincident with virus internalization but without affecting receptor-mediated transferrin uptake. A large amount of the stimulated endocytic activity was macropinocytosis. Macropinocytosis depended on alphav integrins, PKC, F-actin, and the amiloride-sensitive Na+/H+ exchanger, which are all required for Ad escape from endosomes and infection. Macropinocytosis stimulation was not a consequence of viral escape, since it occurred in K44A-dyn-expressing cells. Surprisingly, 30-50% of the endosomal contents were released into the cytosol of control and also K44A-dyn-expressing cells, and the number of fluid phase-positive endosomes dropped below the levels of noninfected cells, indicating macropinosomal lysis. The release of macropinosomal contents was Ad dose dependent, but the presence of Ad particles on macropinosomal membranes was not sufficient for contents release. We conclude that Ad signaling from the cell surface controls the induction of macropinosome formation and leakage, and this correlates with viral exit to the cytosol and infection.
0 downloads since deposited on 11 Feb 2008
25 downloads since 12 months
|Item Type:||Journal Article, refereed|
|Communities & Collections:||07 Faculty of Science > Institute of Molecular Life Sciences|
|DDC:||570 Life sciences; biology|
|Date:||16 September 2002|
|Deposited On:||11 Feb 2008 12:17|
|Last Modified:||27 Nov 2013 20:07|
|Publisher:||Rockefeller University Press|
Users (please log in): suggest update or correction for this item
Repository Staff Only: item control page