PMID:23203805

Citation	Powis, K, Schrul, B, Tienson, H, Gostimskaya, I, Breker, M, High, S, Schuldiner, M, Jakob, U and Schwappach, B (2013) Get3 is a holdase chaperone and moves to deposition sites for aggregated proteins when membrane targeting is blocked. J. Cell. Sci. 126:473-83
Abstract	The endomembrane system of yeast contains different tail-anchored proteins that are post-translationally targeted to membranes via their C-terminal transmembrane domain. This hydrophobic segment could be hazardous in the cytosol if membrane insertion fails, resulting in the need for energy-dependent chaperoning and the degradation of aggregated tail-anchored proteins. A cascade of GET proteins cooperates in a conserved pathway to accept newly synthesized tail-anchored proteins from ribosomes and guide them to a receptor at the endoplasmic reticulum, where membrane integration takes place. It is, however, unclear how the GET system reacts to conditions of energy depletion that might prevent membrane insertion and hence lead to the accumulation of hydrophobic proteins in the cytosol. Here we show that the ATPase Get3, which accommodates the hydrophobic tail anchor of clients, has a dual function: promoting tail-anchored protein insertion when glucose is abundant and serving as an ATP-independent holdase chaperone during energy depletion. Like the generic chaperones Hsp42, Ssa2, Sis1 and Hsp104, we found that Get3 moves reversibly to deposition sites for protein aggregates, hence supporting the sequestration of tail-anchored proteins under conditions that prevent tail-anchored protein insertion. Our findings support a ubiquitous role for the cytosolic GET complex as a triaging platform involved in cellular proteostasis.
Links	PubMed PMC3613179 Online version:10.1242/jcs.112151
Keywords	Adenosine Triphosphatases/metabolism; Carrier Proteins/metabolism; Cell Membrane/metabolism; Guanine Nucleotide Exchange Factors/metabolism; Models, Molecular; Molecular Chaperones/metabolism; Protein Transport; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
YEAST:GET3		GO:1990507: ATP-independent chaperone mediated protein folding	ECO:0000314:		P		Figure 7: Influence of Get3 on the aggregation behavior of citrate synthase (CS)."It is of note that addition of either 2 mM ATP or ADP reproducibly reduced the holdase activity of Get3, implying that Get3 acts most efficiently on these clients in the absence of nucleotides (Fig. 7D)"	complete CACAO 11722

References

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