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.
|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?|