title: α-Adducin translocates to the nucleus upon loss of cell-cell adhesions.
abstract: The F-actin binding protein adducin plays an important role in plasma membrane stability, cell motility and cell-cell junctions. In this study, we demonstrate that α-adducin is mainly localized in the nucleus of sparsely cultured epithelial cells, whereas it is localized at cell-cell junctions when the cells are grown to confluence. Disruption of cell-cell adhesions induces a nuclear translocation of α-adducin. Conversely, α-adducin is redistributed to the cytoplasm and cell-cell junctions in the process of establishing cell-cell adhesions. We identify that α-adducin contains a bipartite nuclear localization signal (NLS) in its COOH-terminal tail domain and a nuclear export signal in its neck region. The phosphorylation of α-adducin at Ser716 that is immediately adjacent to the NLS appears to antagonize the function of the NLS. Moreover, we show that depletion of α-adducin has adverse effects on cell-cell adhesions and, to our surprise, cell proliferation. The impaired cell proliferation is associated with mitotic defects characterized by disorganized mitotic spindles, aberrant chromosomal congregation/segregation and abnormal centrosomes. Taken together, our results not only reveal the mechanism for α-adducin to shuttle between the cytoplasm and nucleus, but also highlight a potential role for α-adducin in mitosis.
authors: Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
authors: Chien-Lin
authors: CL
authors: Chen
authors: Yu-Ping
authors: YP
authors: Lin
authors: Ying-Chu
authors: YC
authors: Lai
authors: Hong-Chen
authors: HC
authors: Chen
mesh_terms: D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D021381:Protein Transport; D014162:Transfection; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D000099291:Adducins