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Evidence for inositol triphosphate as a second messenger for glucose-induced calcium signalling in budding yeast

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Abstract

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 (IP3) in yeast is rapidly transformed into IP4 and IP5 by a dual kinase, Arg82. Then another kinase, Ipk1, phosphorylates the IP5 into IP6. 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. IP3 accumulation upon glucose addition was completely absent in the plc1Δ 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 PIP2 and generation of IP3, seems to be sufficient for raising the calcium level in the cytosol. This is the first indication for a physiological role of IP3 signalling in S. cerevisiae. Many aspects about the signal transduction mechanism and the final effectors require further study.

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Acknowledgements

We thank Laura Popolo, Enrico Ragni, Susan Wente, James York, James Caffrey and Stephen Shears for kindly providing the materials indicated in the Materials and methods. Our particular thanks go to Jan C.T. Bergsma for helpful discussion and advice. This work was supported by grants from the Fund for Scientific Research—Flanders and the Research Fund of the Katholieke Universiteit Leuven (Concerted Research Actions) to S.W., J.W. and J.M.T. and by a grant from FAR (formerly MURST 60%) to E.M.

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Authors and Affiliations

  1. Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Piazza della Scienza 2, 20126, Milan, Italy

    Renata Tisi, Fiorella Belotti & Enzo Martegani

  2. Laboratorium voor Moleculaire Celbiologie, Katholieke Universiteit Leuven and Departement voor Moleculaire Microbiologie, Vlaans Interuniversitair Instituut voor Biotechnologie, Kasteelpark Arenberg 31, 3001, Leuven-Heverlee, Belgium

    Stefaan Wera & Johan M. Thevelein

  3. Functional Biology, Plantkunde en Microbiologie, Katholieke Universiteit Leuven, Kasteelpark Arenberg 31, 3001, Heverlee, Belgium

    Joris Winderickx

Authors
  1. Renata Tisi
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  2. Fiorella Belotti
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  3. Stefaan Wera
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  4. Joris Winderickx
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  5. Johan M. Thevelein
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  6. Enzo Martegani
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Correspondence to Enzo Martegani.

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Communicated by S. Hohmann

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Tisi, R., Belotti, F., Wera, S. et al. Evidence for inositol triphosphate as a second messenger for glucose-induced calcium signalling in budding yeast. Curr Genet 45, 83–89 (2004). https://doi.org/10.1007/s00294-003-0465-5

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  • DOI: https://doi.org/10.1007/s00294-003-0465-5

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