title: ADP-ribosylation factor (ARF)-like 7 (ARL7) is induced by cholesterol loading and participates in apolipoprotein AI-dependent cholesterol export.
abstract: Here, we identify ADP-ribosylation factor (ARF)-like 7 (ARL7) as the only ARF- and ARL-family member whose mRNA-expression is induced by liver X-receptor/retinoid X-receptor agonists or cholesterol loading in human macrophages. Moreover, subcellular distribution of mutant and wild type ARL7-enhanced green fluorescent protein (EGFP) supports that ARL7 may be involved in a vesicular transport step between a perinuclear compartment and the plasma membrane. Therefore, we investigated the effect of ARL7 over-expression on the cholesterol secretory pathway. We found that expression of wild type and dominant active ARL7-EGFP stimulated the rate of apolipoprotein AI-specific cholesterol efflux 1.7- and 2.8-fold. In contrast, expression of the dominant negative form of ARL7-EGFP led to approximately 50% inhibition of cholesterol efflux. This data is consistent with a model in which ARL7 is involved in transport between a perinuclear compartment and the plasma membrane apparently linked to the ABCA1-mediated cholesterol secretion pathway.
authors.affiliation: Institut für Arterioskleroseforschung, Westfälische Wilhelms-Universität, Domagkstr. 3, D-48149 Münster, Germany. engeltho@uni-muenster.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Engel
authors.forename: Aloys
authors.initials: A
authors.lastname: Lueken
authors.forename: Günther
authors.initials: G
authors.lastname: Bode
authors.forename: Uwe
authors.initials: U
authors.lastname: Hobohm
authors.forename: Stefan
authors.initials: S
authors.lastname: Lorkowski
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schlueter
authors.forename: Stephan
authors.initials: S
authors.lastname: Rust
authors.forename: Paul
authors.initials: P
authors.lastname: Cullen
authors.forename: Michael
authors.initials: M
authors.lastname: Pech
authors.forename: Gerd
authors.initials: G
authors.lastname: Assmann
authors.forename: Udo
authors.initials: U
authors.lastname: Seedorf
mesh_terms: D020727:ADP-Ribosylation Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D018168:Receptors, Retinoic Acid / Q000819:agonists; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection
chemical_list: D016632:Apolipoprotein A-I; D008164:Luminescent Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D002784:Cholesterol; D020727:ADP-Ribosylation Factors