title: The protein transportation pathway from Golgi to vacuoles via endosomes plays a role in enhancement of methylmercury toxicity.
abstract: Methylmercury causes serious damage to the central nervous system, but the molecular mechanisms of methylmercury toxicity are only marginally understood. In this study, we used a gene-deletion mutant library of budding yeast to conduct genome-wide screening for gene knockouts affecting the sensitivity of methylmercury toxicity. We successfully identified 31 genes whose deletions confer resistance to methylmercury in yeast, and 18 genes whose deletions confer hypersensitivity to methylmercury. Yeast genes whose deletions conferred resistance to methylmercury included many gene encoding factors involved in protein transport to vacuoles. Detailed examination of the relationship between the factors involved in this transport system and methylmercury toxicity revealed that mutants with loss of the factors involved in the transportation pathway from the trans-Golgi network (TGN) to the endosome, protein uptake into the endosome, and endosome-vacuole fusion showed higher methylmercury resistance than did wild-type yeast. The results of our genetic engineering study suggest that this vesicle transport system (proteins moving from the TGN to vacuole via endosome) is responsible for enhancing methylmercury toxicity due to the interrelationship between the pathways. There is a possibility that there may be proteins in the cell that enhance methylmercury toxicity through the protein transport system.
authors: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors: Gi-Wook
authors: GW
authors: Hwang
authors: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors: Yasutaka
authors: Y
authors: Murai
authors: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors: Tsutomu
authors: T
authors: Takahashi
authors: Laboratory of Molecular and Biochemical Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan.
authors: Akira
authors: A
authors: Naganuma
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D025141:Drug Resistance, Fungal / Q000235:genetics; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D017353:Gene Deletion; D015870:Gene Expression; D015723:Gene Library; D005818:Genetic Engineering; D016681:Genome, Fungal; D008767:Methylmercury Compounds / Q000633:toxicity*; D021381:Protein Transport / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism*; D021601:trans-Golgi Network / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D008767:Methylmercury Compounds; D029701:Saccharomyces cerevisiae Proteins; C004925:methylmercuric chloride