title: Adducin-1 is essential for mitotic spindle assembly through its interaction with myosin-X.
abstract: Mitotic spindles are microtubule-based structures, but increasing evidence indicates that filamentous actin (F-actin) and F-actin-based motors are components of these structures. ADD1 (adducin-1) is an actin-binding protein that has been shown to play important roles in the stabilization of the membrane cortical cytoskeleton and cell-cell adhesions. In this study, we show that ADD1 associates with mitotic spindles and is crucial for proper spindle assembly and mitotic progression. Phosphorylation of ADD1 at Ser12 and Ser355 by cyclin-dependent kinase 1 enables ADD1 to bind to myosin-X (Myo10) and therefore to associate with mitotic spindles. ADD1 depletion resulted in distorted, elongated, and multipolar spindles, accompanied by aberrant chromosomal alignment. Remarkably, the mitotic defects caused by ADD1 depletion were rescued by reexpression of ADD1 but not of an ADD1 mutant defective in Myo10 binding. Together, our findings unveil a novel function for ADD1 in mitotic spindle assembly through its interaction with Myo10.
authors.affiliation: Department of Life Sciences, 2 Graduate Institute of Molecular Biology, 3 Graduate Institute of Biomedical Sciences, 4 Agricultural Biotechnology Center, and 5 Rong-Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan.
authors.forename: Po-Chao
authors.initials: PC
authors.lastname: Chan
authors.forename: Rosaline Y C
authors.initials: RY
authors.lastname: Hsu
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Liu
authors.forename: Chien-Chen
authors.initials: CC
authors.lastname: Lai
authors.forename: Hong-Chen
authors.initials: HC
authors.lastname: Chen
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D020090:Chromosome Segregation; D004285:Dogs; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D009218:Myosins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000099291:Adducins
chemical_list: D016203:CDC2 Protein Kinase; D002148:Calmodulin-Binding Proteins; D009218:Myosins; D000099291:Adducins; C498718:MYO10 protein, human