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Two ras pathways in fission yeast are differentially regulated by two ras guanine nucleotide exchange factors

Piyi Papadaki1, Véronique Pizon, Brian Onken

  • 1Biology Department, New York University, New York, New York 10003-6688, USA.

Molecular and Cellular Biology
|June 8, 2002
PubMed

Insights

Efc25 is a guanine nucleotide exchange factor (GEF) specific to the Ras1-Scd1 pathway in yeast, controlling cell morphology. Ste6 GEF specifically activates the Ras1-Byr2 pathway for mating.

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Yeast genetics

Background:

  • Ras proteins are key regulators of cellular signaling.
  • Ras1 in Schizosaccharomyces pombe has two distinct downstream pathways: one for morphogenesis and chromosome segregation (via Scd1) and another for mating (via Byr2).
  • Ste6 is the only known guanine nucleotide exchange factor (GEF) for Ras1, but ste6 mutants only affect mating, suggesting another GEF exists for the Scd1 pathway.

Purpose of the Study:

  • To identify and characterize a novel GEF responsible for activating the Ras1-Scd1 pathway.
  • To elucidate the specific roles of Efc25 and Ste6 in regulating Ras1 signaling.
  • To understand how GEF expression influences the segregation of Ras1 signaling outputs.

Main Methods:

  • Genetic analysis, including null mutants (e.g., ste6 Delta, efc25 Delta) and synthetic lethality assays.
  • Protein truncation studies to identify functional domains.
  • Gene expression analysis (constitutive vs. induced).
  • Overexpression studies to assess pathway dominance.

Main Results:

  • Efc25 was identified as a GEF that functions upstream of the Ras1-Scd1 pathway, but not the Ras1-Byr2 pathway.
  • Efc25's GEF domain is essential and regulated by its N-terminus.
  • Efc25 expression is constitutive, unlike Ste6 which is induced during mating.
  • Efc25 overexpression leads to hyperelongated cells and sterility, while Ste6 overexpression can inhibit Scd1 activation.

Conclusions:

  • Efc25 acts as a specific GEF for the Ras1-Scd1 pathway, controlling morphogenesis.
  • Differential expression of GEFs (Efc25 and Ste6) allows for the segregation of Ras1 signaling outputs.
  • GEFs play a crucial role in coupling Ras proteins to specific downstream effectors, thereby fine-tuning cellular responses.

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