Substrate‐mediated remodeling of methionine transport by multiple ubiquitin‐dependent mechanisms in yeast cells

Plasma membrane transport of single amino‐acid methionine in yeast is shown to be mediated by at least seven different permeases whose activities are transcriptionaly and post‐transcriptionaly regulated by different ubiquitin‐dependent mechanisms. Upon high extracellular methionine exposure, three methionine‐permease genes are repressed while four others are induced. SCFMet30, SCFGrr1 and Rsp5 ubiquitin ligases are the key actors of the ubiquitin‐dependent remodeling of methionine transport. In addition to regulating the activity of Met4, the SCFMet30 ubiquitin ligase is shown to convey an intracellular signal to a membrane initiated signaling pathway by controlling the nuclear concentration of the Stp1 transcription factor. By coupling intra‐ and extracellular metabolite sensing, SCFMet30 thus allows yeast cells to accurately adjust the intermediary sulfur metabolism to the growth conditions. The multiple ubiquitin‐dependent mechanisms that function in methionine transport regulation further exemplify the pervasive role of ubiquitin in the adaptation of single‐cell organisms to environmental modifications.

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