Compartmentalized signaling of Ras in fission yeast

doi:10.1073/pnas.0603318103

Compartmentalized signaling of Ras in fission yeast

*Department of Molecular and Cell Biology, The Breast Center, Baylor College of Medicine, 1 Baylor Plaza, BCM 600, Houston, TX 77030; and
^†Department of Medicine, Cell Biology, and Pharmacology, New York University School of Medicine, 550 1st Avenue, New York, NY 10016

Communicated by Michael H. Wigler, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, April 26, 2006 (received for review November 29, 2005)

Abstract

Compartment-specific Ras signaling is an emerging paradigm that may explain the multiplex outputs from a single GTPase. The fission yeast, Schizosaccharomyces pombe, affords a simple system in which to study Ras signaling because it has a single Ras protein, Ras1, that regulates two distinct pathways: one that controls mating through a Byr2-mitogen-activated protein kinase cascade and one that signals through Scd1-Cdc42 to maintain elongated cell morphology. We generated Ras1 mutants that are restricted to either the endomembrane or the plasma membrane. Protein binding studies showed that each could interact with the effectors of both pathways. However, when examined in ras1 null cells, endomembrane-restricted Ras1 supported morphology but not mating, and, conversely, plasma membrane-restricted Ras1 supported mating but did not signal to Scd1-Cdc42. These observations provide a striking demonstration of compartment-specific Ras signaling and indicate that spatial specificity in the Ras pathway is evolutionarily conserved.

Footnotes

^‡To whom correspondence may be addressed. E-mail: philim01{at}med.nyu.edu or echang{at}breastcenter.tmc.edu
Author contributions: B.O., M.R.P., and E.C.C. designed research; B.O., H.W., M.R.P., and E.C.C. performed research; B.O., M.R.P., and E.C.C. contributed new reagents/analytical tools; B.O., M.R.P., and E.C.C. analyzed data; and B.O., M.R.P., and E.C.C. wrote the paper.
Conflict of interest statement: No conflicts declared.
Abbreviations:

Abbreviations:

CFP,

cyan fluorescent protein;

ER,

endoplasmic reticulum;

GAD,

Gal4 activation domain;

PM,

plasma membrane;

RitC,

C terminus of Rit;

YFP,

yellow fluorescent protein.