ADP-ribosylation factor (ARF)-like 7 (ARL7) is induced by cholesterol loading and participates in apolipoprotein AI-dependent cholesterol export.
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.
Engel
Thomas
T
Institut für Arterioskleroseforschung, Westfälische Wilhelms-Universität, Domagkstr. 3, D-48149 Münster, Germany. engeltho@uni-muenster.de
Lueken
Aloys
A
Bode
Günther
G
Hobohm
Uwe
U
Lorkowski
Stefan
S
Schlueter
Bernhard
B
Rust
Stephan
S
Cullen
Paul
P
Pech
Michael
M
Assmann
Gerd
G
Seedorf
Udo
U
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
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