Cruz-Garcia, D., Ortega-Bellido, M., Scarpa, M., Villeneuve, J., Jovic, M., Porzner, M., Balla, T., Seufferlein, T., Malhotra, V. (2013). Recruitment of arfaptins to the trans-Golgi network by PI(4)P and their involvement in cargo export.  EMBO J. 32(12): 1717--1729.

FBrf0222322

Research paper

The BAR (Bin/Amphiphysin/Rvs) domain proteins arfaptin1 and arfaptin2 are localized to the trans-Golgi network (TGN) and, by virtue of their ability to sense and/or generate membrane curvature, could play an important role in the biogenesis of transport carriers. We report that arfaptins contain an amphipathic helix (AH) preceding the BAR domain, which is essential for their binding to phosphatidylinositol 4-phosphate (PI(4)P)-containing liposomes and the TGN of mammalian cells. The binding of arfaptin1, but not arfaptin2, to PI(4)P is regulated by protein kinase D (PKD) mediated phosphorylation at Ser100 within the AH. We also found that only arfaptin1 is required for the PKD-dependent trafficking of chromogranin A by the regulated secretory pathway. Altogether, these findings reveal the importance of PI(4)P and PKD in the recruitment of arfaptins at the TGN and their requirement in the events leading to the biogenesis of secretory storage granules.

PMC3680738 (PMC) (EuropePMC)