Zinc and the Msc2 zinc transporter protein are required for endoplasmic reticulum function.
In this report, we show that zinc is required for endoplasmic reticulum function in Saccharomyces cerevisiae. Zinc deficiency in this yeast induces the unfolded protein response (UPR), a system normally activated by unfolded ER proteins. Msc2, a member of the cation diffusion facilitator (CDF) family of metal ion transporters, was previously implicated in zinc homeostasis. Our results indicate that Msc2 is one route of zinc entry into the ER. Msc2 localizes to the ER when expressed at normal levels. UPR induction in low zinc is exacerbated in an msc2 mutant. Genetic and biochemical evidence indicates that this UPR induction is due to genuine ER dysfunction. Notably, we found that ER-associated protein degradation is defective in zinc-limited msc2 mutants. We also show that the vacuolar CDF proteins Zrc1 and Cot1 are other pathways of ER zinc acquisition. Finally, zinc deficiency up-regulates the mammalian ER stress response indicating a conserved requirement for zinc in ER function among eukaryotes.
Department of Biochemistry, University of Missouri, Columbia 65211, USA.
Charissa D
CD
Ellis
Fudi
F
Wang
Colin W
CW
MacDiarmid
Suzanne
S
Clark
Thomas
T
Lyons
David J
DJ
Eide
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D017930:Genes, Reporter; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
C076223:COT1 protein, S cerevisiae; D002352:Carrier Proteins; D027682:Cation Transport Proteins; C429021:MSC2 protein, S cerevisiae; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; C088843:ZRC1 protein, S cerevisiae; D015032:Zinc