Nuclear trafficking

Daniel Püntener
Markus Eisenhut
Olmo Sonzogni

The functional organisation of the nucleus is one of the least understood topics in cell biology. Static images of the nucleus suggest a highly ordered entity but recent dynamic analyses using photobleaching techniques show that most nuclear proteins, including the chromatin mass are mobile and the interaction of proteins with chromatin is highly dynamic. The mechanisms by which nuclear components move and are confined has implications on gene regulations in cell growth of development and disease. We ask the question how does the incoming adenovirus DNA-genome translocate through the nuclear pores into the nucleus and how does it traffick in the nucleoplasm to establish epichromosomal replication domains.

Image4: Adenovirus capsid disassembly and nuclear import through the nuclear pore complex.

The capsid disassembly process is irreversible and therefore tightly controlled by the virus. It serves to deliver the uncoated viral DNA genome into the nucleus with nanoprecision. A partly uncoated viral capsid is released from the microtubules and handed over to the nuclear pore complex, the gate keeper of the nucleus. The pore complex filament protein CAN/Nup214 serves as an attachment site, positioning the capsid at the center of the pore and thereby exposing it to nuclear factors, including the linker histone H1.2 to trigger disassembly.


Key publications:

Greber, U.F., Suomalainen, M., Stidwill, R.P., Boucke, K., Ebersold, M., and Helenius, A. (1997). The role of the nuclear pore complex in adenovirus DNA entry. EMBO J. 16, 5998-6007.     pubmed   (PDF, 487 KB)
 
Trotman, L.C., Mosberger, N., Fornerod, M., Stidwill, R.P., and Greber, U.F. (2001). Import of adenovirus DNA involves the nuclear pore complex receptor CAN/Nup214 and histone H1. Nature Cell Biology 3, 1092-1100.     pubmed   (PDF, 3696 KB)
 
Greber, U.F., and Fassati, A. (2003). Nuclear import of viral DNA genomes. Traffic 4, 136-143.     pubmed