Ca2+ signal is generated only once in the mating pheromone response pathway in Saccharomyces cerevisiae.
The mating pheromone, alpha-factor, of the yeast Saccharomyces cerevisiae binds to the heterotrimeric G protein-coupled cell surface receptor of MATa cells and induces cellular responses necessary for mating. In higher eukaryotic cells, many hormones and growth factors rapidly mobilize a second messenger, Ca2+, by means of receptor-G protein signaling. Although striking similarities between the mechanisms of the receptor-G protein signaling in yeast and higher eukaryotes have long been known, it is still uncertain whether the pheromone rapidly mobilizes Ca2+ necessary for early events of the pheromone response. Here we reexamine this problem using sensitive methods for detecting Ca2+ fluxes and mobilization, and find no evidence that there is rapid Ca2+ influx leading to a rapid increase in the cytosolic free Ca2+ concentration. In addition, the yeast PLC1 deletion mutant lacking phosphoinositide-specific phospholipase C, a key enzyme for generating Ca2+ signals in higher eukaryotic cells, responds normally to the pheromone. These findings suggest that the receptor-G protein signaling does not utilize Ca2+ as a second messenger in the early stage of the pheromone response pathway. Since the receptor-G protein signaling does stimulate Ca2+ influx after early events have finished and this stimulation is essential for late events in the pheromone response pathway [Iida et al., (1990) J. Biol. Chem., 265: 13391-13399] Ca2+ may be used only once in the signal transduction pathway in unicellular eukaryotes such as yeast.
Nakajima-Shimada
J
J
Department of Parasitology, Juntendo University School of Medicine, Tokyo, Japan.
Sakaguchi
S
S
Tsuji
F I
FI
Anraku
Y
Y
Iida
H
H
D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D000072235:Mating Factor; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D015290:Second Messenger Systems; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000235:genetics
D010455:Peptides; D011956:Receptors, Cell Surface; D000072235:Mating Factor; D010738:Type C Phospholipases; D020962:Heterotrimeric GTP-Binding Proteins; D002118:Calcium