The nuclear export factor Xpo1p targets Mad1p to kinetochores in yeast.
Nuclear pore complexes (NPCs) mediate all nucleocytoplasmic traffic and provide docking sites for the spindle assembly checkpoint (SAC) protein Mad1p. Upon SAC activation, Mad1p is recruited onto kinetochores and rapidly cycles between NPCs and kinetochores. We examined the mechanism of Mad1p movement onto kinetochores and show that it is controlled by two components of the nuclear transport machinery, the exportin Xpo1p and Ran-guanosine triphosphate (GTP). Mad1p contains a nuclear export signal (NES) that is recognized by Xpo1p. The NES, Xpo1p, and RanGTP are all required for Mad1p recruitment onto kinetochores in checkpoint-activated cells. Consistent with this function, Xpo1p also accumulates on kinetochores after SAC activation. We have also shown that Xpo1p and RanGTP are required for the dynamic cycling of Mad1p between NPCs and kinetochores in checkpoint-arrested cells. These results reveal an important function for Xpo1p in mediating intranuclear transport events and identify a signaling pathway between kinetochores and NPCs.
Scott
Robert J
RJ
Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
Cairo
Lucas V
LV
Van de Vosse
David W
DW
Wozniak
Richard W
RW
D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D028884:Karyopherins / Q000378:metabolism / Q000502:physiology*; D018386:Kinetochores / Q000378:metabolism*; D022022:Nuclear Pore / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D021382:Protein Sorting Signals; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism; D015003:Yeasts / Q000166:cytology / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000378:metabolism; D000097606:Exportin 1 Protein
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D028884:Karyopherins; D009687:Nuclear Proteins; D021382:Protein Sorting Signals; D018160:Receptors, Cytoplasmic and Nuclear; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein