MAP kinase signaling induces nuclear reorganization in budding yeast

Background: During the mating pheromone response in budding yeast, activati on of a mitogen-activated protein kinase (MAP kinase) cascade results in we ll-characterized changes in cytoskeletal organization and gene expression. Spatial reorganization of genes within the nucleus has been documented duri ng cell-type differentiation in mammalian cells, but no information was pre viously available on the morphology of the yeast nucleus during the major t ranscriptional reprogramming that accompanies zygote formation. Results: We find that in response to mating pheromone, budding yeast nuclei assume an unusual dumbbell shape, reflecting a spatial separation of chrom osomal and nucleolar domains. Within the chromosomal domain, telomeric foci persist and maintain their associated complement of Sir proteins. The nucl eolus, on the other hand, assumes a novel cup-shaped morphology and a posit ion distal to the mating projection tip. Although microtubules are required for this orientation with respect to the projection tip, neither microtubu les nor actin polymerization are necessary for the observed changes in nucl ear shape. We find that activation of the pheromone-response MAP kinase pat hway by ectopic expression of STE4 or STE11 leads to identical nuclear and nucleolar reorganization in the absence of pheromone. Mutation of downstrea m effector MAP kinases Fus3p and Kss1p, or of the transcriptional regulator Ste12p, blocks nuclear shape changes, whereas overexpression of Ste12p pro motes dumbbell-shaped nuclei in the absence of pheromone. Conclusions: Nuclear remodeling occurs when the MAP kinase cascade is activ ated by yeast pheromone, but it is independent of the cytoskeletal reorgani zation regulated by the same signaling pathway. Activation of the Ste12p tr anscription factor is necessary, and may be sufficient, for the changes in nuclear structure that coincide with developmentally significant changes in gene expression. (C) 2000 Elsevier Science Ltd. All rights reserved.