TIP47, a lipid cargo protein involved in macrophage triglyceride metabolism.
OBJECTIVE
Uptake of lipids by macrophages (MPhi) leads to lipid droplet accumulation and foam cell formation. The PAT family proteins are implicated in lipid droplet formation, but the precise function of the 47-kDa tail interacting protein (TIP47), a member of this family, is poorly defined. The present study was performed to determine the function of TIP47 in MPhi lipid metabolism.


RESULTS
Freeze-fracture cytochemistry demonstrates that TIP47 is present in the plasma membrane of MPhi and is aggregated into clusters when the cells are incubated with oleate. Suppression of adipophilin levels using siRNA knockdown leads to migration of TIP47 from a cytoplasmic pool to the lipid droplet. Further, reduction of TIP47 decreases triglyceride levels, whereas raising TIP47 levels by expression of EGFP-TIP47 shows the opposite effect.


CONCLUSIONS
Our results show that the TIP47 protein levels directly correlate with triglyceride levels. We propose that TIP47 may act as a carrier protein for free fatty acids and in this way participates in conversion of MPhi into foam cells.
Buers
Insa
I
Leibniz Institute for Arteriosclerosis Research, Domagkstr. 3, 48149 Muenster, Germany. i_buer01@uni-muenster.de
Robenek
Horst
H
Lorkowski
Stefan
S
Nitschke
Yvonne
Y
Severs
Nicholas J
NJ
Hofnagel
Oliver
O
D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism*; D000070796:Perilipin-3; D011257:Pregnancy Proteins / Q000502:physiology*; D014280:Triglycerides / Q000378:metabolism*; D033921:Vesicular Transport Proteins
D004268:DNA-Binding Proteins; D005230:Fatty Acids, Nonesterified; D047908:Intracellular Signaling Peptides and Proteins; C038196:PLIN3 protein, human; D000070796:Perilipin-3; D011257:Pregnancy Proteins; D014280:Triglycerides; D033921:Vesicular Transport Proteins