Abstract #68

ATG1 regulates filamentous growth independent of autophagy in Saccharomyces cerevisiae. Montrell D Seay, Michael Snyder, Savithramma Dinesh-Kumar. MCDB, Yale University, New Haven, CT.
   In response to nitrogen limitation, diploid Saccharomyces cerevisiae utilize two distinct signaling mechanisms for survival: pseudohyphal growth and autophagy. Moderately low nitrogen concentrations triggers diploid cells to undergo pseudohyphal differentiation characterized by protein translation and modifications, elongated cells that remain attached following cytokinesis. Extremely low nitrogen concentrations trigger cells to cease pseudohyphal growth and undergo bulk protein degradation or autophagy for cell survival. Although these distinct processes operate within a relatively narrow physiological range of nitrogen availability, they must be stringently controlled to prevent cross activation yet flexible enough to facilitate a rapid and fluid response during nitrogen consumption. Here we present evidence that ATG1, a serine/theronine kinase required for autophagy, is also needed for pseudohyphae formation. -/-apg1mutant strains are unable to undergo pseudohyphal differentiation in response to low nitrogen. By contrast over expression of GST-ATG induces pseudohyphal growth irrespective of nitrogen concentrations. This novel role of ATG1 is independent of autophagy since pseudohyphae production proceeds during ATG1 over expression in a -/-atg14 background although autophagy is inhibited. Several studies including epistasis analysis, proteome array analysis and in vitro kinase assays indicate that ATG1 is downstream of the MAPKK Ste7 and the MAPK KSS, known regulators of pseudohyphae growth. Furthermore, we show that ATG1 functions through TEC1, a master regulator of pseudohyphae growth. It has previously been shown that the kinase activity of ATG1 is not required for autophagy. Here we demonstrate that the kinase activity of ATG1 is indispensable for proper pseudohyphae formation. Finally we propose a novel model for nitrogen sensing that utilizes ATG1 as a molecular switch: the MAPK-activated ATG1 utilizes its kinase activity to induce pseudohyphae while the mTOR-mediated inactivation of ATG1 activates autophagy while inhibiting pseudohyphae formation.

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