Non-Canonical Regulation of Phosphatidylserine Metabolism by a Phosphatidylinositol Transfer Protein and a Phosphatidylinositol 4-OH Kinase

Wang, Y.; Yuan, P.; Tripathi, A.; Rodriguez, M.; Lonnfors, M.; Eisenberg-Bord, M.; Schuldiner, M.; Bankaitis, V.

doi:10.1101/696336

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bioRxiv · 10.1101/696336

Non-Canonical Regulation of Phosphatidylserine Metabolism by a Phosphatidylinositol Transfer Protein and a Phosphatidylinositol 4-OH Kinase

Wang, Y.·Yuan, P.·Tripathi, A.·Rodriguez, M.·Lonnfors, M.·Eisenberg-Bord, M.·Schuldiner, M.·Bankaitis, V.

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Abstract

The phosphatidylserine (PtdSer) decarboxylase Psd2 is proposed to engage in an endoplasmic reticulum (ER)-Golgi/endosome membrane contact site (MCS) that facilitates phosphatidylserine decarboxylation to phosphatidylethanomaine (PtdEtn) in Saccharomyces cerevisiae. While this MCS is envisioned to consist of Psd2, the Sec14-like phosphatidylinositol transfer protein (PITP) Sfh4, the Stt4 phosphatidylinositol (PtdIns) 4-OH kinase, the Scs2 tether, and at least one other uncharacterized protein, functional data that address key foundations of this model are sparse. We now report that Psd2, Sfh4 and Stt4 are the only components individually required for biologically sufficient Psd2-dependent PtdEtn production. Surprisingly, neither the PtdIns-transfer activity of Sfh4 nor its capacity to activate Stt4 is required to stimulate the Psd2 pathway. Instead, Sfh4 activates the Psd2 pathway via a specific Sfh4-Psd2 physical interaction. Whereas the data indicate an Sfh4-independent association of Stt4 with Psd2 as well, we find Stt4 also regulates Psd2 activity indirectly by influencing the PtdSer pool accessible to Psd2 for decarboxylation. These collective results demonstrate that the proposed ER-Golgi/endosomal MCS model fails to provide an accurate description of the Psd2 system in yeast, and provide an example where the biological function of a Sec14-like PITP is uncoupled from its canonical activity as a PtdIns transfer protein.

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Wang, Y., Yuan, P., Tripathi, A., Rodriguez, M., Lonnfors, M., Eisenberg-Bord, M., Schuldiner, M., Bankaitis, V.. 2019-07-08. Non-Canonical Regulation of Phosphatidylserine Metabolism by a Phosphatidylinositol Transfer Protein and a Phosphatidylinositol 4-OH Kinase. https://doi.org/10.1101/696336

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