title: The Nuclear Transport Factor Kap121 Is Required for Stability of the Dam1 Complex and Mitotic Kinetochore Bi-orientation.
abstract: The karyopherin (Kap) family of nuclear transport factors facilitates macromolecular transport through nuclear pore complexes (NPCs). The binding of Kaps to their cargos can also regulate, both temporally and spatially, the interactions of the cargo protein with interacting partners. Here, we show that the essential yeast Kap, Kap121, binds Dam1 and Duo1, components of the microtubule (MT)-associated Dam1 complex required for linking dynamic MT ends with kinetochores (KTs). Like mutations in the Dam1 complex, loss of Kap121 function compromises the formation of normal KT-MT attachments during mitosis. We show that the stability of the Dam1 complex in vivo is dependent on its association with Kap121. Furthermore, we show that the Kap121/Duo1 complex is maintained in the presence of RanGTP but Kap121 is released by the cooperative actions of RanGTP and tubulin. We propose that Kap121 stabilizes the Dam1 complex and participates in escorting it to spindle MTs.
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada.
authors.forename: Lucas V
authors.initials: LV
authors.lastname: Cairo
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada. Electronic address: rick.wozniak@ualberta.ca.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Wozniak
mesh_terms: D021581:Active Transport, Cell Nucleus; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D011485:Protein Binding; D055550:Protein Stability; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C116003:DAM1 protein, S cerevisiae; C116004:DUO1 protein, S cerevisiae; D026901:Membrane Transport Proteins; D008869:Microtubule-Associated Proteins; C483822:PSE1 protein, S cerevisiae; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D014404:Tubulin; D020931:ran GTP-Binding Protein
keywords: Dam1 complex; Duo1; Kap121; Ran; chromosome segregation; karyopherin; kinetochore