title: Saccharomyces cerevisiae Grx6 and Grx7 are monothiol glutaredoxins associated with the early secretory pathway.
abstract: Saccharomyces cerevisiae Grx6 and Grx7 are two monothiol glutaredoxins whose active-site sequences (CSYS and CPYS, respectively) are reminiscent of the CPYC active-site sequence of classical dithiol glutaredoxins. Both proteins contain an N-terminal transmembrane domain which is responsible for their association to membranes of the early secretory pathway vesicles, facing the luminal side. Thus, Grx6 localizes at the endoplasmic reticulum and Golgi compartments, while Grx7 is mostly at the Golgi. Expression of GRX6 is modestly upregulated by several stresses (calcium, sodium, and peroxides) in a manner dependent on the Crz1-calcineurin pathway. Some of these stresses also upregulate GRX7 expression under the control of the Msn2/4 transcription factor. The N glycosylation inhibitor tunicamycin induces the expression of both genes along with protein accumulation. Mutants lacking both glutaredoxins display reduced sensitivity to tunicamycin, although the drug is still able to manifest its inhibitory effect on a reporter glycoprotein. Grx6 and Grx7 have measurable oxidoreductase activity in vivo, which is increased in the presence of tunicamycin. Both glutaredoxins could be responsible for the regulation of the sulfhydryl oxidative state at the oxidant conditions of the early secretory pathway vesicles. However, the differences in location and expression responses against stresses suggest that their functions are not totally overlapping.
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Facultat de Medicina, Universitat de Lleida, Montserrat Roig 2, 25008 Lleida, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Izquierdo
authors.forename: Celia
authors.initials: C
authors.lastname: Casas
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mühlenhoff
authors.forename: Christopher Horst
authors.initials: CH
authors.lastname: Lillig
authors.forename: Enrique
authors.initials: E
authors.lastname: Herrero
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000502:physiology; D054477:Glutaredoxins / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D022142:Secretory Vesicles / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C532450:GRX7 protein, S cerevisiae; D054477:Glutaredoxins; C527470:Grx6 protein, S cerevisiae; C081935:MSN2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D050862:Oxidoreductases Acting on Sulfur Group Donors; C080499:sulfide oxidase