PKA-dependent dynein switching from lysosomes to adenovirus: a novel form of host-virus competition.
Cytoplasmic dynein is responsible for transport of several viruses to the nucleus. Adenovirus recruits dynein directly. Transport depends on virus-induced activation of protein kinase A (PKA) and other cellular protein kinases, whose roles in infection are poorly understood. We find that PKA phosphorylates cytoplasmic dynein at a novel site in light intermediate chain 1 (LIC1) that is essential for dynein binding to the hexon capsid subunit and for virus motility. Surprisingly, the same LIC1 modification induces a slow, but specific, dispersal of lysosomes (lyso)/late endosomes (LEs) that is mediated by inhibition of a newly identified LIC1 interaction with the RILP (Rab7-interacting lysosomal protein). These results identify an organelle-specific dynein regulatory modification that adenovirus uses for its own transport. PKA-mediated LIC1 phosphorylation causes only partial lyso/LE dispersal, suggesting a role for additional, parallel mechanisms for dynein recruitment to lyso/LEs. This arrangement provides a novel means to fine tune transport of these organelles in response to infection as well as to developmental and physiological cues.
Department of Pathology and Cell Biology, Columbia University, New York, NY 10032.
Julian
J
Scherer
Julie
J
Yi
Richard B
RB
Vallee
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000256:Adenoviridae / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000235:genetics; D002213:Capsid / Q000378:metabolism*; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D056445:Cytoplasmic Dyneins / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D051381:Rats
D048868:Adaptor Proteins, Signal Transducing; C557700:RILP protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases; C486042:Dync1li1 protein, rat; D056445:Cytoplasmic Dyneins