Mitosis-specific regulation of nuclear transport by the spindle assembly checkpoint protein Mad1p

Mol Cell. 2013 Jan 10;49(1):109-20. doi: 10.1016/j.molcel.2012.10.017. Epub 2012 Nov 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Aurora Kinases
  • Cell Cycle Checkpoints
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / physiology*
  • Cell Nucleus / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kinetochores / metabolism
  • Membrane Transport Proteins / metabolism
  • Metaphase*
  • Microtubules / metabolism*
  • Mitosis
  • Nuclear Pore / metabolism
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Phosphorylation
  • Protein Binding
  • Protein Phosphatase 1 / metabolism
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Spindle Apparatus / metabolism

Substances

  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • MAD1 protein, S cerevisiae
  • Membrane Transport Proteins
  • Nuclear Proteins
  • PSE1 protein, S cerevisiae
  • Receptors, Cytoplasmic and Nuclear
  • Saccharomyces cerevisiae Proteins
  • Aurora Kinases
  • IPL1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • MPS1 protein, S cerevisiae
  • GLC7 protein, S cerevisiae
  • Protein Phosphatase 1