Localization of Ras signaling complex in budding yeast

Biochimica Et Biophysica Acta
Fiorella BelottiEnzo Martegani

Abstract

In Saccharomyces cerevisiae, cAMP/pKA pathway plays a major role in metabolism, stress resistance and proliferation control. cAMP is produced by adenylate cyclase, which is activated both by Gpr1/Gpa2 system and Ras proteins, regulated by Cdc25/Sdc25 guanine exchange factors and Ira GTPase activator proteins. Recently, both Ras2 and Cdc25 RasGEF were reported to localize not only in plasma membrane but also in internal membranes. Here, the subcellular localization of Ras signaling complex proteins was investigated both by fluorescent tagging and by biochemical cell membrane fractionation on sucrose gradients. Although a consistent minor fraction of Ras signaling complex components was found in plasma membrane during exponential growth on glucose, Cdc25 appears to localize mainly on ER membranes, while Ira2 and Cyr1 are also significantly present on mitochondria. Moreover, PKA Tpk1 catalytic subunit overexpression induces Ira2 protein to move from mitochondria to ER membranes. These data confirm the hypothesis that different branches of Ras signaling pathways could involve different subcellular compartments, and that relocalization of Ras signaling complex components is subject to PKA control.

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Citations

Feb 4, 2014·FEMS Microbiology Reviews·Michaela ConradJohan M Thevelein
Nov 7, 2012·The International Journal of Biochemistry & Cell Biology·Serena BroggiSonia Colombo
Aug 12, 2017·Cell Death and Differentiation·Jeffrey KnuppAmy Chang
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Aug 31, 2018·FEMS Yeast Research·Nicoletta GuaragnellaSergio Giannattasio
Jul 1, 2020·Cell Discovery·Roberto QuadriMarco Muzi-Falconi
Jun 24, 2021·Cell Discovery·Roberto QuadriMarco Muzi-Falconi

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