Endocytosis and signalling

Michele Gastaldelli
Nicola Imelli
Karin Boucke

Endocytosis is driven by vesicle formation at the plasma membrane and follows the same routes as uptake of nutrients, extracellular medium, membranes and cell surface proteins. It is a major entry gate for pathogens into cells and serves important functions in anti-microbial and anti-viral responses by the host immune system. Incoming adenovirus type 2 or 5 enter by clathrin-mediated endocytosis and activate clathrin-independent macropinocytosis. Both of these endocytic processes require the viral coreceptor alpha v integrin. Macropinocytosis is not essential for viral uptake but macropinosomal contents of infected cells are released into the cytosol, indicating that adenovirus regulates the cellular machinery controlling endosomal leakiness. This correlates with endosomal exit of virus and infection. We are analyzing the mechanisms of endosomal lysis triggered by adenovirus.

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Image 2a: Clathrin-mediated endocytosis of adenovirus serotype 2 triggers macropinocytosis and macropinosomal lysis.   Image 2b: The escape of phagosomal adenovirus targeted to the Fc-gamma receptor of hematopoietic cells requires late stages of clathrin-coated pit formation.

Key publications:

Nakano, M.Y., Boucke, K., Suomalainen, M., Stidwill, R.P., and Greber, U.F. (2000). The first step of adenovirus type 2 disassembly occurs at the cell surface, independently of endocytosis and escape to the cytosol. J Virol 74, 7085-7095.     pubmed   (PDF, 2719 KB)
   
Meier, O., Boucke, K., Vig, S., Keller, S., Stidwill, R.P., Hemmi, S., and Greber, U.F. (2002). Adenovirus triggers macropinocytosis and endosomal leakage together with its clathrin mediated uptake. J. Cell Biol. 158, 1119-1131.     pubmed   (PDF, 776 KB)
   
Meier, O., and Greber, U.F. (2003). Adenovirus endocytosis. J. Gene Med. 5, 451–462.     pubmed  
   
Imelli, N., Meier, O., Boucke, K., Hemmi, S., and Greber, U.F. (2004). Cholesterol is required for endocytosis and endosomal escape of Adenovirus type 2. J. Virol. 78, 3089-3098.     pubmed  
   
Meier, O., Gastaldelli, M., Boucke, K., Hemmi, S., and Greber, U.F. (2005). Early steps of clathrin-mediated endocytosis involved in phagosomal escape of Fc-g receptor targeted adenovirus. J. Virol. 79, 2604-2613.     pubmed