A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP.
Intracellular lipid traffic is mediated both by membrane vesicles and by a number of non-vesicular pathways facilitated by cytoplasmic lipid binding proteins. For these proteins to act effectively they must be targeted accurately to specific membranes. Here we identify a novel short conserved determinant called the FFAT motif that is shared by several seemingly unrelated lipid binding proteins and is also found in Opi1p, a transcriptional regulator of phospholipid synthesis in yeast. FFAT motifs act as membrane- targeting determinants by their direct interaction with homologues of VAMP-associated protein (VAP), a conserved endoplasmic reticulum (ER) protein. In budding yeast, all four proteins with FFAT motifs interact with Scs2p, a homologue of VAP, to target the ER to some extent. The precise intracellular distribution of each of these proteins depends on the integration of the FFAT-Scs2p interaction with other targeting determinants, and the interaction is functionally significant. We conclude that binding to a VAP homologue is a common mechanism by which proteins with FFAT motifs, most of which are involved in lipid metabolism, target ER membranes.
Loewen
Christopher J R
CJ
Division of Cell Biology, Institute of Ophthalmology, University College London, Bath Street, London EC1V 9EL, UK.
Roy
Anjana
A
Levine
Timothy P
TP
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D050356:Lipid Metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
C096105:OPI1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins