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Cytoplasmic transport

Sten Strunze
Markus Eisenhut
Karin Boucke

Molecular crowding restricts the diffusion of macromolecules in the cytoplasm. Many cargo complexes use motors for effective cytoplasmic trafficking. Long range transport of cellular cargo is typically mediated by microtubules and microtubule-associated motors of the kinesin and dynein families. It is largely unknown how loading and unloading of motors to cargo occurs. Microorganisms and many viruses prominently abuse the microtubule shuttling system. In the case of adenovirus, two distinct virus-activated signalling pathways are involved in microtubule-dependent viral motility. An integrin-dependent activation of protein kinase A and integrin-independent activation of the p38/MAPK stress cascade ensure that trafficking of incoming virus is biased towards the minus ends of the microtubules at the microtubule-nucleating centrosome. How these signalling events are connected to the recruitment of the dynein/dynactin motor complex, to detachment and activation of the dynein motor or additional motors is subject to our studies.

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Image 3a: Arrest of adenovirus particles at the microtubule-organizing centrosome of interphase cells in the absence of nuclear export induced by the export inhibitor leptomycin B.   Image 3b: How does the incoming adenovirus detach from the microtubule tracks to reach the nuclear membrane and avoid trapping at the centrosome?

Key publications:

Suomalainen, M., Nakano, M.Y., Boucke, K., Keller, S., Stidwill, R.P., and Greber, U.F. (1999). Microtubule-dependent minus and plus end-directed motilities are competing processes for nuclear targeting of adenovirus. J. Cell Biol. 144, 657-672.
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Suomalainen, M., Nakano, M.Y., Boucke, K., Keller, S., and Greber, U.F. (2001). Adenovirus-activated PKA and p38/MAPK pathways boost microtubule-mediated nuclear targeting of virus. Embo J 20, 1310-1319.
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Mabit, H., Nakano, M.Y., Prank, U., Saam, B., Döhner, K., Sodeik, B., and Greber, U.F. (2002). Intact microtubules support Adenovirus and Herpes simplex virus infections. J. Virol. 76, 9962-9971.
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Strunze, S., Trotman, L.C., Boucke, K., and Greber, U.F. (2005). Nuclear targeting of Adenovirus requires CRM1-mediated nuclear export. Mol Biol Cell in press.
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Greber, U.F. (2005). Viral trafficking violations in axons - the herpes virus case. Proc. Natl. Acad. Sci. USA in press.
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