Background & aims: α-taxilin was identified as binding partner of syntaxins and is supposed to regulate vesicular trafficking. However, the physiological functions of α-taxilin and its potential relevance for the life cycle of hepatitis B virus (HBV) are still poorly understood.
Methods: Transfected hepatoma cells, infected primary human hepatocytes, and liver tissue of HBV-infected patients were used to study the expression of α-taxilin. Subcellular localization and colocalization were analyzed by confocal laser scanning microscopy (CLSM). Protein-protein interactions were further investigated by co-immunoprecipitations. Silencing of α-taxilin expression was performed by lentiviral gene transfer.
Results: HBV producing cells show a significant higher level of α-taxilin. HBV induces α-taxilin expression, by its regulatory proteins HBx and LHBs via c-Raf. This indicates that α-taxilin is essential for the release of HBV particles. CLSM and co-immunoprecipitations demonstrated that the PreS1PreS2 domain of LHBs interacts with α-taxilin. α-taxilin harbors a YXXL motif that represents a classic late domain. In accordance with this, it was found by co-immunoprecipitations that α-taxilin interacts with the ESCRT I component tsg101. CLSM revealed that a fraction of α-taxilin colocalizes with LHBs and tsg101.
Conclusions: α-taxilin plays an essential role for release of HBV-DNA containing particles. It might act as an adapter that binds, on the one hand, to LHBs and, on the other hand, to tsg101 and thereby helps recruit the ESCRT machinery to the viral envelope proteins.
Keywords: CLSM; EIAV; ESCRT; HBV; HBx; HCC; LHBs; MVB; Morphogenesis; RCC; SHBs; SVP; Signal transduction; TXLN; confocal laser scanning microscopy; endosomal sorting complex required for transport; equine infective anemia virus; hepatitis B virus; hepatocellular carcinoma; large hepatitis B virus surface antigen; multivesicular body; renal cell carcinoma; small ….; subviral particle; tdn; transdominant negative; α-taxilin gene.
Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.