Serum albumin promotes ATP-binding cassette transporter-dependent sterol uptake in yeast
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Serum albumin promotes ATP-binding cassette transporter-dependent sterol uptake in yeast. / Marek, Magdalena; Silvestro, Daniele; Fredslund, Maria D.; Andersen, Tonni G.; Günther-Pomorski, Thomas.
I: FEMS Yeast Research, Bind 14, Nr. 8, 2014, s. 1223-1233.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Serum albumin promotes ATP-binding cassette transporter-dependent sterol uptake in yeast
AU - Marek, Magdalena
AU - Silvestro, Daniele
AU - Fredslund, Maria D.
AU - Andersen, Tonni G.
AU - Günther-Pomorski, Thomas
PY - 2014
Y1 - 2014
N2 - Sterol uptake in fungi is a multistep process that involves interaction between external sterols and the cell wall, incorporation of sterol molecules into the plasma membrane, and subsequent integration into intracellular membranes for turnover. ATP-binding cassette (ABC) transporters have been implicated in sterol uptake, but key features of their activity remain to be elucidated. Here, we apply fluorescent cholesterol (NBD-cholesterol) to monitor sterol uptake under anaerobic and aerobic conditions in two fungal species, Candida glabrata (Cg) and Saccharomyces cerevisiae (Sc). We found that in both fungal species, ABC transporter-dependent uptake of cholesterol under anaerobic conditions and in mutants lacking HEM1 gene is promoted in the presence of the serum protein albumin that is able to bind the sterol molecule. Furthermore, the C. glabrataABC transporter CgAus1p expressed in S. cerevisiae requires the presence of serum or albumin for efficient cholesterol uptake. These results suggest that albumin can serve as sterol donor in ABC transporter-dependent sterol uptake, a process potentially important for growth of C. glabrata inside infected humans.
AB - Sterol uptake in fungi is a multistep process that involves interaction between external sterols and the cell wall, incorporation of sterol molecules into the plasma membrane, and subsequent integration into intracellular membranes for turnover. ATP-binding cassette (ABC) transporters have been implicated in sterol uptake, but key features of their activity remain to be elucidated. Here, we apply fluorescent cholesterol (NBD-cholesterol) to monitor sterol uptake under anaerobic and aerobic conditions in two fungal species, Candida glabrata (Cg) and Saccharomyces cerevisiae (Sc). We found that in both fungal species, ABC transporter-dependent uptake of cholesterol under anaerobic conditions and in mutants lacking HEM1 gene is promoted in the presence of the serum protein albumin that is able to bind the sterol molecule. Furthermore, the C. glabrataABC transporter CgAus1p expressed in S. cerevisiae requires the presence of serum or albumin for efficient cholesterol uptake. These results suggest that albumin can serve as sterol donor in ABC transporter-dependent sterol uptake, a process potentially important for growth of C. glabrata inside infected humans.
KW - Aerobic exclusion
KW - Cholesterol
KW - Functional complementation
KW - Heterologous expression
KW - Pathogenic yeast
KW - Sterol scavenging
U2 - 10.1111/1567-1364.12219
DO - 10.1111/1567-1364.12219
M3 - Journal article
C2 - 25331273
AN - SCOPUS:84918570037
VL - 14
SP - 1223
EP - 1233
JO - FEMS Yeast Research
JF - FEMS Yeast Research
SN - 1567-1356
IS - 8
ER -
ID: 130638050