title: Identification of FEZ1 as a protein that interacts with JC virus agnoprotein and microtubules: role of agnoprotein-induced dissociation of FEZ1 from microtubules in viral propagation.
abstract: The human polyomavirus JC virus (JCV) is the causative agent of a fatal demyelinating disease, progressive multifocal leukoencephalopathy, and encodes six major proteins, including agnoprotein. Agnoprotein colocalizes with microtubules in JCV-infected cells, but its function is not fully understood. We have now identified fasciculation and elongation protein zeta 1 (FEZ1) as a protein that interacted with JCV agnoprotein in a yeast two-hybrid screen of a human brain cDNA library. An in vitro binding assay showed that agnoprotein interacted directly with FEZ1 and microtubules. A microtubule cosedimentation assay revealed that FEZ1 also associates with microtubules and that agnoprotein induces the dissociation of FEZ1 from microtubules. Agnoprotein inhibited the promotion by FEZ1 of neurite outgrowth in PC12 cells. Conversely, overexpression of FEZ1 suppressed JCV protein expression and intracellular trafficking in JCV-infected cells. These results suggest that FEZ1 promotes neurite extension through its interaction with microtubules, and that agnoprotein facilitates JCV propagation by inducing the dissociation of FEZ1 from microtubules.
authors.affiliation: Laboratory of Molecular and Cellular Pathology, School of Medicine, Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Sapporo, Japan.
authors.forename: Tadaki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Okada
authors.forename: Shingo
authors.initials: S
authors.lastname: Semba
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Orba
authors.forename: Satoko
authors.initials: S
authors.lastname: Yamanouchi
authors.forename: Shuichi
authors.initials: S
authors.lastname: Endo
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.forename: Toshitsugu
authors.initials: T
authors.lastname: Fujita
authors.forename: Shun'ichi
authors.initials: S
authors.lastname: Kuroda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nagashima
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D007577:JC Virus / Q000737:chemistry*; D051379:Mice; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism; D008957:Models, Genetic; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000737:chemistry; D054334:Viral Regulatory and Accessory Proteins; D000086082:Viroporin Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D005982:Glutathione Transferase; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C528597:FEZ1 protein, human; C118711:LZTS1 protein, human; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins