Evidence for inositol triphosphate as a second messenger for glucose-induced calcium signalling in budding yeast.
The Saccharomyces cerevisiae phospholipase C Plc1 is involved in cytosolic transient glucose-induced calcium increase, which also requires the Gpr1/Gpa2 receptor/G protein complex and glucose hexokinases. Differing from mammalian cells, this increase in cytosolic calcium concentration is mainly due to an influx from the external medium. No inositol triphosphate receptor homologue has been identified in the S. cerevisiae genome; and, therefore, the transduction mechanism from Plc1 activation to calcium flux generation still has to be identified. Inositol triphosphate (IP(3)) in yeast is rapidly transformed into IP(4) and IP(5) by a dual kinase, Arg82. Then another kinase, Ipk1, phosphorylates the IP(5) into IP(6). In mutant cells that do not express either of these kinases, the glucose-induced calcium signal was not only detectable but was even wider than in the wild-type strain. IP(3) accumulation upon glucose addition was completely absent in the plc1Delta strain and was amplified both by deletion of either ARG82 or IPK1 genes and by overexpression of PLC1. These results taken together suggest that Plc1p activation by glucose, leading to cleavage of PIP(2) and generation of IP(3), seems to be sufficient for raising the calcium level in the cytosol. This is the first indication for a physiological role of IP(3) signalling in S. cerevisiae. Many aspects about the signal transduction mechanism and the final effectors require further study.
Tisi
Renata
R
Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, Italy.
Belotti
Fiorella
F
Wera
Stefaan
S
Winderickx
Joris
J
Thevelein
Johan M
JM
Martegani
Enzo
E
D020013:Calcium Signaling / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D005800:Genes, Fungal; D005947:Glucose / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism
D029701:Saccharomyces cerevisiae Proteins; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; C425775:ARG82 protein, S cerevisiae; C120127:IPK1 protein, S cerevisiae; D017853:Phosphotransferases (Alcohol Group Acceptor); D010738:Type C Phospholipases; C432456:phospholipase C1; D005947:Glucose