The localization of nuclear exporters of the importin-beta family is regulated by Snf1 kinase, nutrient supply and stress.
In the budding yeast Saccharomyces cerevisiae, four members of the importin-beta family of nuclear carriers, Xpo1p/Crm1p, Cse1p, Msn5p and Los1p, function as exporters of protein and tRNA. Under normal growth conditions GFP-tagged exporters are predominantly associated with nuclei. The presence of Snf1 kinase, a key regulator of cell growth and a metabolic sensor, controls the localization of GFP-exporters. Additional glucose-dependent, but Snf1-independent, mechanisms regulate carrier distribution and a switch from fermentable to non-fermentable carbon sources relocates all of the carriers, suggesting a link to the nutritional status of the cell. Moreover, stress controls the proper localization of GFP-exporters, which mislocalize upon exposure to heat, ethanol and starvation. Stress may activate the MAPK cell integrity cascade, and we tested the role of this pathway in exporter localization. Under non-stress conditions, the proper distribution of GFP-Cse1p and Xpo1p/Crm1p-GFP requires kinases of the cell integrity cascade. By contrast, Msn5p-GFP and Los1p-GFP rely on the MAPK module to relocate to the cytoplasm when cells are stressed with ethanol. Our results indicate that the association of nuclear exporters with nuclei is controlled by multiple mechanisms that are organized in a hierarchical fashion and linked to the physiological state of the cell.
Quan
XinXin
X
Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada.
Yu
Jennifer
J
Bussey
Howard
H
Stochaj
Ursula
U
D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000903:Antibiotics, Antineoplastic / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus / Q000378:metabolism; D028961:beta Karyopherins / Q000235:genetics / Q000378:metabolism*; D000097606:Exportin 1 Protein
D000903:Antibiotics, Antineoplastic; D002244:Carbon; D000431:Ethanol; D028884:Karyopherins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D017346:Protein Serine-Threonine Kinases; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D020123:Sirolimus; D028961:beta Karyopherins; D000097606:Exportin 1 Protein; C082274:CSE1 protein, S cerevisiae; C408090:Los1 protein, S cerevisiae; C401306:MSN5 protein, S cerevisiae; C071570:SNF1-related protein kinases