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Ruotolo R, et al.  (2008) Membrane transporters and protein traffic networks differentially affecting metal tolerance: a genomic phenotyping study in yeast. Genome Biol 9(4):R67

Abstract: ABSTRACT: BACKGROUND: The cellular mechanisms underlying metal toxicity and detoxification are extremely variegated and incompletely understood. Genomic phenotyping was used to assess the role of all non-essential S. cerevisiae proteins in modulating cell viability after exposure to cadmium, nickel and other metals. RESULTS: A number of novel genes and pathways affecting multimetal as well as metal-specific tolerance were discovered. Although the vacuole emerged as a major hot-spot for metal detoxification, we also identified a number of pathways playing a more general, less direct role in promoting cell survival under stress conditions (e.g., mRNA decay, nucleo-cytoplasmic transport and iron acquisition) as well as proteins more proximally related to metal damage prevention or repair. Most prominent among the latter are various nutrient transporters previously not associated with metal toxicity. A strikingly differential effect was observed for a large set of deletions, the majority of which centred on the ESCRT and retromer complexes, that by affecting transporter downregulation and intracellular protein traffic cause cadmium sensitivity, but nickel resistance. CONCLUSIONS: The data show that a previously underestimated variety of pathways are involved in cadmium and nickel tolerance in eukaryotic cells. As revealed by comparison with five additional metals, there is a good correlation between the chemical properties and the cellular toxicity signatures of different metals. However, many conserved pathways centred on membrane transporters and protein traffic affect cell viability with a surprisingly high degree of metal specificity.

Status: Published Type: Journal Article PubMed ID: 18394190

Topics addressed in this paper

Number of different genes curated to this paper: 158

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Topics Topics not linked to Genes Genes linked to topics (#1 - 10 )
AAT2 AFT1 ALF1 APL5 APL6 APM3 APS3 ARO2 BCK1 BUB3
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Topics Genes linked to topics (#11 - 20 )
CCC2 CCR4 CDC10 CLC1 CLN3 CSF1 CTI6 CTK1 CTK3 CTR1
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Topics Genes linked to topics (#21 - 30 )
CUE1 CYS4 DBF2 DRS2 EOS1 ERG2 ERG24 ERG6 ERV41 ERV46
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Topics Genes linked to topics (#31 - 40 )
FAB1 FET3 FET4 FIG4 FTR1 FUR4 FYV7 GET3 HDA1 HUR1
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Topics Genes linked to topics (#41 - 50 )
ICE2 ILM1 LSM7 MAC1 MAL31 MAM3 MFT1 MGA2 MOG1 MTC4
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Topics Genes linked to topics (#51 - 60 )
MTC6 MUD1 NNF2 NPL3 NRG1 NUP120 NUP170 NUP188 NUP84 PAT1
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Topics Genes linked to topics (#61 - 70 )
PBS2 PEP12 PEP3 PEP5 PEP8 PHO84 PHO85 PHO86 PHO88 PHO89
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Topics Genes linked to topics (#71 - 80 )
PKR1 POP2 PTC1 RAD6 RAV1 RIM101 RIM13 RIM20 ROX1 RPB9
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Topics Genes linked to topics (#81 - 90 )
RPL14A RPN4 RPS1A RRN10 RTF1 RTT103 SAC3 SAC6 SAM37 SAP190
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Topics Genes linked to topics (#91 - 100 )
SCP160 SHP1 SIF2 SIN3 SIS2 SIW14 SLA1 SLT2 SMF1 SMF2
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Topics Genes linked to topics (#101 - 110 )
SMF3 SMP1 SNF12 SNF5 SNF8 SNX3 SPC72 SPT7 SRB8 STE24
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Topics Genes linked to topics (#111 - 120 )
SWI3 TAT1 TED1 THP1 THP2 TNA1 UBC7 UBP3 UME6 URE2
Alias blue ball
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Topics Genes linked to topics (#121 - 130 )
VAC14 VAM3 VAM6 VAM7 VMA1 VMA10 VMA11 VMA13 VMA16 VMA2
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Topics Genes linked to topics (#131 - 140 )
VMA21 VMA22 VMA3 VMA4 VMA5 VMA6 VMA7 VMA8 VMA9 VPH1
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Topics Genes linked to topics (#141 - 150 )
VPH2 VPS16 VPS28 VPS30 VPS35 VPS41 VPS5 VPS51 VTC1 VTC4
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Topics Genes linked to topics (#151 - 158 )
WHI3 XRN1 YBT1 YCF1 YCK3 YDJ1 YMR010W ZRT3
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