PPIP5K1 interacts with the exocyst complex through a C-terminal intrinsically disordered domain and regulates cell motility.

Cellular signaling involves coordinated regulation of many events. Scaffolding proteins are crucial regulators of cellular signaling, because they are able to affect numerous events by coordinating specific interactions among multiple protein partners in the same pathway. Scaffolding proteins often contain intrinsically disordered regions (IDR) that facilitate the formation and function of distinct protein complexes. We show that PPIP5K1 contains an unusually long and evolutionarily conserved IDR. To investigate the biological role(s) of this domain, we identified interacting proteins using affinity purification coupled with mass spectrometry. Here, we report that PPIP5K1 is associated with a network of proteins that regulate vesicle-mediated transport. We further identified exocyst complex component 1 as a direct interactor with the IDR of PPIP5K1. Additionally, we report that knockdown of PPIP5K1 decreases motility of HeLa cells in a wound-healing assay. These results suggest that PPIP5K1 might play an important role in regulating function of exocyst complex in establishing cellular polarity and directional migration of cells.