title: Lipid transfer proteins do their thing anchored at membrane contact sites… but what is their thing?
abstract: Membrane contact sites are structures where two organelles come close together to regulate flow of material and information between them. One type of inter-organelle communication is lipid exchange, which must occur for membrane maintenance and in response to environmental and cellular stimuli. Soluble lipid transfer proteins have been extensively studied, but additional families of transfer proteins have been identified that are anchored into membranes by transmembrane helices so that they cannot diffuse through the cytosol to deliver lipids. If such proteins target membrane contact sites they may be major players in lipid metabolism. The eukaryotic family of so-called Lipid transfer proteins Anchored at Membrane contact sites (LAMs) all contain both a sterol-specific lipid transfer domain in the StARkin superfamily (related to StART/Bet_v1), and one or more transmembrane helices anchoring them in the endoplasmic reticulum (ER), making them interesting subjects for study in relation to sterol metabolism. They target a variety of membrane contact sites, including newly described contacts between organelles that were already known to make contact by other means. Lam1-4p target punctate ER-plasma membrane contacts. Lam5p and Lam6p target multiple contacts including a new category: vacuolar non-NVJ cytoplasmic ER (VancE) contacts. These developments confirm previous observations on tubular lipid-binding proteins (TULIPs) that established the importance of membrane anchored proteins for lipid traffic. However, the question remaining to be solved is the most difficult of all: are LAMs transporters, or alternately are they regulators that affect traffic more indirectly?
authors.affiliation: Department of Cell Biology, UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, U.K.
authors.forename: Louise H
authors.initials: LH
authors.lastname: Wong
authors.affiliation: Department of Cell Biology, UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, U.K. tim.levine@ucl.ac.uk.
authors.forename: Tim P
authors.initials: TP
authors.lastname: Levine
mesh_terms: D017360:Arabidopsis / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C030363:lipid transfer protein
keywords: biological transport; ergosterol/analogues and derivatives/chemistry; intracellular membranes/*metabolism; membrane lipids/metabolism; proteins/genetics/*metabolism; proteins/genetics/metabolism; saccharomyces cerevisiae; vesicular transport