The Nutrient Stress-induced Small GTPase Rab5 Contributes to the Activation of Vesicle Trafficking and Vacuolar Activity

Abstract

Background: How the function of Rab5 isoforms is regulated remains unclear. Results: The third Rab5 isoform, Ypt53, is up-regulated significantly under nutrient stress. Conclusion:The up-regulated Ypt53 and the constitutive Vps21 are crucial for vesicle transport and vacuolar hydrolase activity, and they prevent ROS accumulation and mitochondrial dysfunction. Significance: The function of three Rab5 isoforms may be regulated differently to adapt to environmental changes.

Regulation of Rab5 isoforms by transcriptional and post‐transcriptional mechanisms in yeast

“…We demonstrate that Vps21 is the most abundant and Ypt53 the least abundant Rab5 protein in yeast. This had been predicted earlier based on theoretical codon usage and indirect assays . We show that the induction of Ypt53 requires the TFs Crz1 and Gis1 in a nonredundant manner.…”

“…HA-Ypt52 levels declined during starvation. After 24 h HA-Ypt53 protein levels were upregulated as reported earlier [17] and increased even further with ongoing starvation, but always remained considerably lower than HA-Vps21 (compare lanes 4,8,12 in Fig. S1H).…”

“…In summary, Ypt53 is able to exert all functions of the major Rab5 isoform Vps21 as reported earlier [12,17], provided it is expressed at protein levels close to or above native Vps21 expression levels. However, at very low expression levels, only Vps21 but not Ypt53 can maintain sufficient Rab5 activity to promote growth and endosomal protein sorting.…”

“…Calcium‐induced transcription of YPT53 via Crz1 was previously demonstrated . Gis1 mediates gene expression upon diauxic shift and entry into G 0 (stationary phase) , and promotes YPT53 expression in postlog cells . Also the induction of Ypt53 in endosomal sorting mutants requires Crz1 and Gis1.…”

“…The TFs Crz1 and Gis1 are required for induction of YPT53 in response to calcium treatment or upon entry into stationary phase . Both Gis1 and Crz1 were also indispensable for the efficient upregulation of Ypt53 in response to nitrogen starvation (Fig.…”