TorC1 and nitrogen catabolite repression control of integrated GABA shunt and retrograde pathway gene expression.

Abstract

Despite our detailed understanding of how the lower GABA shunt and retrograde genes are regulated, there is a paucity of validated information concerning control of GAD1, the glutamate decarboxylase gene which catalyzes the first reaction of the GABA shunt. Further, integration of glutamate degradation via the GABA shunt has not been investigated. Here, we show that while GAD1 shares a response to rapamycin-inhibition of the TorC1 kinase, it does so independently of the Gln3 and Gat1 NCR-sensitive transcriptional activators that mediate transcription of the lower GABA shunt genes. We also show that GABA shunt gene expression increases dramatically in response to nickel ions. The α-ketoglutarate needed for the GABA shunt to cycle, thereby producing reduced pyridine nucleotides, derives from the retrograde pathway as shown by a similar high increase in the retrograde reporter, CIT2 when nickel is present in the medium. These observations demonstrate high integration of the GABA shunt, retrograde, peroxisomal glyoxylate cycle, and β-oxidation pathways.