title: Mitosis-specific regulation of nuclear transport by the spindle assembly checkpoint protein Mad1p.
abstract: Nuclear pore complexes (NPCs) and kinetochores perform distinct tasks, yet their shared ability to bind several proteins suggests their functions are intertwined. Among these shared proteins is Mad1p, a component of the yeast spindle assembly checkpoint (SAC). Here we describe a role for Mad1p in regulating nuclear import that employs its ability to sense a disruption of kinetochore-microtubule interactions during mitosis. We show that kinetochore-microtubule detachment arrests nuclear import mediated by the transport factor Kap121p through a mechanism that requires Mad1p cycling between unattached, metaphase kinetochores and binding sites at the NPC. This signaling pathway requires the Aurora B-like kinase Ipl1p, and the resulting transport changes inhibit the nuclear import of Glc7p, a phosphatase that acts as an Ipl1p antagonist. We propose that a distinct branch of the SAC exists in which Mad1p senses unattached kinetochores and, by altering NPC transport activity, regulates the nuclear environment of the spindle.
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors.forename: Lucas V
authors.initials: LV
authors.lastname: Cairo
authors.forename: Christopher
authors.initials: C
authors.lastname: Ptak
authors.forename: Richard W
authors.initials: RW
authors.lastname: Wozniak
mesh_terms: D021581:Active Transport, Cell Nucleus; D064127:Aurora Kinases; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008677:Metaphase; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis; D022022:Nuclear Pore / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D054645:Protein Phosphatase 1 / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; C501382:MAD1 protein, S cerevisiae; D026901:Membrane Transport Proteins; D009687:Nuclear Proteins; C483822:PSE1 protein, S cerevisiae; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D064127:Aurora Kinases; C576961:IPL1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C093416:MPS1 protein, S cerevisiae; C092048:GLC7 protein, S cerevisiae; D054645:Protein Phosphatase 1