No abstract

SUMMARY Early in infection, adenovirus travels to the nucleus as a naked capsid using the microtubule motor cytoplasmic dynein. This study was initiated to address how the virus recruits dynein, and to explore the role of dynein's diverse regulatory factors in virus transport. Cytoplasmic dynein, dynactin and NudE/NudEL, but not LIS1 or ZW10, colocalized with incoming, post-endosomal adenovirus particles. Dynein alone interacted in a pH-dependent manner with the adenovirus subunit hexon, which, in turn, interacted with recombinant dynein intermediate chain and light intermediate chain 1. Interference with dynactin function had no effect on dynein colocalization with adenovirus, but reduced virus run length. Expression of hexon or injection of anti-hexon antibody inhibited virus transport without affecting Golgi distribution. These results identify hexon as a direct receptor for cytoplasmic dynein, which recruits dynein for transport to the nucleus by a mechanism both novel and distinct from that for known physiological dynein cargo forms.

Background: Cytoplasmic dynein performs a great variety of cellular functions using a diversity of regulators. Results: NudE and dynactin compete for a common site within the dynein complex. Conclusion: This mechanism prevents dual regulation by dynactin and LIS1 and suggests a major new mode of regulatory control. Significance: This is the first insight into coordination of cytoplasmic dynein regulators.

How cytoplasmic dynein is recruited to diverse organelles remains incompletely understood. Using the first subcellular localization of LIC isoforms, along with RNAi, RILP, and dynactin dominant negatives, the LIC subunits are found to recruit dynein specifically to components of the late endocytic pathway through a dynactin-independent mechanism.

PKA-mediated phosphorylation of a specific residue in the dynein light intermediate chain 1 releases the motor protein from lysosomes and late endosomes while activating its recruitment to adenovirus capsids.