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Updated: Aug 21, 2026

Genome-wide Protein-protein Interaction Screening by Protein-fragment Complementation Assay (PCA) in Living Cells
Published on: March 3, 2015
[The double-play of PP17/TIP47]
Alain Pauloin1, Michèle Ollivier-Bousquet, Eric Chanat
1Unité de Génomique et physiologie de la lactation, Inra, 78352 Jouy-en-Josas, France. pauloin@jouy.inra.fr
Abstract:
A missing link in the understanding of the mechanisms of transport of the mannose 6-phosphate receptors has recently been discovered, following the identification of the protein TIP47. In association with Rab9-GTP, this protein is responsible for the return of the receptors from the late endosomes back to the trans-Golgi network. Curiously, the same protein called PP17b, was described as a placental protein twenty years ago, and more recently, as a blood marker for human uterine cervical cancer. The sequence of PP17b/TIP47 displays not only a strong homology with those of adipophilin and the perilipins, two proteins known to be involved in the intracellular traffic of lipid droplets but also PP17b/TIP47 is associated with the later. How this ubiquitous protein could participate in processes as different as the mannose 6-phosphate receptors traffic and the formation and/or traffic of lipid droplets? A tentative hypothesis is put forward.
Insights
The protein TIP47, also known as PP17b, is crucial for transporting mannose 6-phosphate receptors. This ubiquitous protein also plays a role in lipid droplet traffic, suggesting a dual function in cellular processes.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Mannose 6-phosphate receptors are essential for lysosomal enzyme targeting.
- The intracellular transport mechanisms of these receptors are not fully understood.
- TIP47 (also known as PP17b) has been identified as a key player in receptor recycling.
Purpose of the Study:
- To elucidate the role of TIP47 in the retrograde transport of mannose 6-phosphate receptors.
- To investigate the potential dual functions of TIP47 in both receptor trafficking and lipid metabolism.
- To explore the homology of TIP47 with lipid droplet-associated proteins.
Main Methods:
- Protein identification and characterization.
- Analysis of protein-protein interactions (e.g., with Rab9-GTP).
- Homology studies comparing TIP47 with adipophilin and perilipins.
- Investigation of TIP47's association with lipid droplets.
Main Results:
- TIP47, in complex with Rab9-GTP, mediates the return of mannose 6-phosphate receptors from late endosomes to the trans-Golgi network.
- TIP47 shares sequence homology with lipid droplet proteins (adipophilin, perilipins) and is associated with lipid droplets.
- Previous studies identified PP17b (homologous to TIP47) as a placental protein and a cancer biomarker.
Conclusions:
- TIP47 is a multifunctional protein involved in distinct cellular transport pathways.
- The discovery of TIP47's role provides a missing link in understanding mannose 6-phosphate receptor trafficking.
- A hypothesis is proposed regarding how TIP47 integrates roles in receptor and lipid droplet transport.
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