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Published on: April 1, 2014
TIP47 functions in the biogenesis of lipid droplets
Anna V Bulankina1, Anke Deggerich, Dirk Wenzel
1Institute for Biochemistry II, University of Göttingen, 37073 Göttingen, Germany.
Abstract:
TIP47 (tail-interacting protein of 47 kD) was characterized as a cargo selection device for mannose 6-phosphate receptors (MPRs), directing their transport from endosomes to the trans-Golgi network. In contrast, our current analysis shows that cytosolic TIP47 is not recruited to organelles of the biosynthetic and endocytic pathways. Knockdown of TIP47 expression had no effect on MPR distribution or trafficking and did not affect lysosomal enzyme sorting. Therefore, our data argue against a function of TIP47 as a sorting device. Instead, TIP47 is recruited to lipid droplets (LDs) by an amino-terminal sequence comprising 11-mer repeats. We show that TIP47 has apolipoprotein-like properties and reorganizes liposomes into small lipid discs. Suppression of TIP47 blocked LD maturation and decreased the incorporation of triacylglycerol into LDs. We conclude that TIP47 functions in the biogenesis of LDs.
Insights
Tail-interacting protein of 47 kD (TIP47) does not sort mannose 6-phosphate receptors. Instead, TIP47 is crucial for lipid droplet (LD) biogenesis and maturation, reorganizing lipids to form small discs.
Area of Science:
- Cell Biology
- Molecular Biology
- Lipid Metabolism
Background:
- Tail-interacting protein of 47 kD (TIP47) was previously thought to be a cargo selection device for mannose 6-phosphate receptors (MPRs).
- Its proposed role involved directing MPR transport from endosomes to the trans-Golgi network for lysosomal enzyme sorting.
Purpose of the Study:
- To investigate the actual function of TIP47 in cellular transport and sorting pathways.
- To determine the role of TIP47 in the context of lipid metabolism and organelle biogenesis.
Main Methods:
- TIP47 knockdown experiments to assess effects on MPR distribution and lysosomal enzyme sorting.
- Analysis of TIP47 recruitment to cellular organelles, particularly lipid droplets (LDs).
- Biochemical assays to characterize TIP47's interaction with lipids and its effect on liposome structure.
Main Results:
- Cytosolic TIP47 was not recruited to endosomes or the Golgi apparatus.
- TIP47 knockdown did not impact MPR trafficking or lysosomal enzyme sorting.
- TIP47 was identified as a lipid droplet-associated protein, recruited via its amino-terminal 11-mer repeats.
- TIP47 demonstrated apolipoprotein-like properties, restructuring liposomes into smaller lipid discs.
- Suppression of TIP47 impaired LD maturation and reduced triacylglycerol incorporation into LDs.
Conclusions:
- TIP47 does not function as a sorting device for MPRs.
- TIP47 plays a critical role in the biogenesis and maturation of lipid droplets.
- TIP47's apolipoprotein-like activity is essential for its function in LD formation.
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