Article
- The EMBO Journal (2005) 24, 2989 - 2999
- doi:10.1038/sj.emboj.7600764
Published online: 11 August 2005
Subject Categories:
AAA ATPases regulate membrane association of yeast oxysterol binding proteins and sterol metabolism
Penghua Wang1, Yong Zhang1, Hongzhe Li1, Hai Kee Chieu1, Alan L Munn2,3,4 and Hongyuan Yang1
- Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore, Singapore
- Institute of Molecular and Cell Biology, A*STAR Biomedical Research Institutes, Singapore, Singapore
- Institute for Molecular Bioscience and ARC Special Research Centre for Functional and Applied Genomics, The University of Queensland, St Lucia, Queensland, Australia
- School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia
Correspondence to:
Hongyuan Yang, Department of Biochemistry, National University of Singapore, Singapore 119260, Singapore. Tel.: +65 687 47996; Fax: +65 677 91453; E-mail: bchyangr@nus.edu.sg
Received 18 November 2004; Accepted 13 July 2005
Abstract
The yeast genome encodes seven oxysterol binding protein homologs, Osh1p–Osh7p, which have been implicated in regulating intracellular lipid and vesicular transport. Here, we show that both Osh6p and Osh7p interact with Vps4p, a member of the AAA (ATPases associated with a variety of cellular activities) family. The coiled-coil domain of Osh7p was found to interact with Vps4p in a yeast two-hybrid screen and the interaction between Osh7p and Vps4p appears to be regulated by ergosterol. Deletion of VPS4 induced a dramatic increase in the membrane-associated pools of Osh6p and Osh7p and also caused a decrease in sterol esterification, which was suppressed by overexpression of OSH7. Lastly, overexpression of the coiled-coil domain of Osh7p (Osh7pCC) resulted in a multivesicular body sorting defect, suggesting a dominant negative role of Osh7pCC possibly through inhibiting Vps4p function. Our data suggest that a common mechanism may exist for AAA proteins to regulate the membrane association of yeast OSBP proteins and that these two protein families may function together to control subcellular lipid transport.
Keywords:
- AAA ATPase,
- lipid transport,
- oxysterol binding protein (OSBP)
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