TY - JOUR
T1 - Noncanonical regulation of phosphatidylserine metabolism by a Sec14-like protein and a lipid kinase
AU - Wang, Yaxi
AU - Yuan, Peihua
AU - Grabon, Aby
AU - Tripathi, Ashutosh
AU - Lee, Dongju
AU - Rodriguez, Martin
AU - Lonnfors, Max
AU - Eisenberg-Bord, Michal
AU - Wang, Zehua
AU - Lam, Sin Man
AU - Schuldiner, Maya
AU - Bankaitis, Vytas A.
N1 - V.A. Bankaitis dedicates this work to the memory of the incomparable Lina Obeid. We are grateful to W. Scott Moye-Rowley (Department of Molecular Medicine, University of Iowa, Iowa City, IA) for his generous gifts of yeast strains and plasmids and for his helpful discussions regarding Psd2 localization experiments. This work was supported by grants from the National Institutes of Health (R35 GM131804) to V.A. Bankaitis. The M. Schuldiner laboratory is supported by the Deutsche Forschungsgemeinschaft (SFB1190; Compartmental gates and contact sites) and a Volkswagen Foundation Life grant. M. Schuldiner is an incumbent of the Dr. Gilbert Omenn and Martha Darling Professorial Chair in Molecular Genetics. M. Eisenberg-Bord is supported by a PhD fellowship from the Azrieli Foundation. Author contributions: Conceptualization: Y. Wang, P. Yuan, A. Tripathi, V.A. Bankaitis; Investigation: Y. Wang, P. Yuan, A. Grabon, A. Tripathi, D. Lee, M. Rodriguez, M. Lönnfors, M. Eisenberg-Bord, Z. Wang, S.M. Lam, M. Schuldiner, V.A. Bankaitis; Visualization: Y. Wang, P. Yuan, A. Tripathi, M. Rodriguez, M. Lönnfors, M. Eisenberg-Bord, M. Schuldiner, V.A. Bankaitis; Writing – Original Draft: Y. Wang, V.A. Bankaitis; Writing – Review and editing Y. Wang, P. Yuan, A. Tripathi, M. Lönnfors, M. Eisenberg-Bord, Z. Wang, S.M. Lam, M. Schuldiner, V.A. Bankaitis: Supervision: Y. Wang, P. Yuan, A. Tripathi, M. Lönnfors, S.M. Lam, M. Schuldiner, V.A. Bankaitis; Funding Acquisition: M. Schuldiner, V.A. Bankaitis.
PY - 2020/5/4
Y1 - 2020/5/4
N2 - The yeast phosphatidylserine (PtdSer) decarboxylase Psd2 is proposed to engage in a membrane contact site (MCS) for PtdSer decarboxylation to phosphatidylethanolamine (PtdEtn). This proposed MCS harbors Psd2, the Sec14-like phosphatidylinositol transfer protein (PITP) Sfh4, the Stt4 phosphatidylinositol (Ptdlns) 4-OH kinase, the Scs2 tether, and an uncharacterized protein. We report that, of these components, only Sfh4 and Stt4 regulate Psd2 activity in vivo. They do so via distinct mechanisms. Sfh4 operates via a mechanism for which its Ptdlns-transfer activity is dispensable but requires an Sfh4-Psd2 physical interaction. The other requires Stt4-mediated production of Ptdlns-4-phosphate (PtdIns4P), where Stt4 (along with the Sad PtdIns4P phosphatase and endoplasmic reticulum-plasma membrane tethers) indirectly modulate Psd2 activity via a PtdIns4P homeostatic mechanism that influences PtdSer accessibility to Psd2. These results identify an example in which the biological function of a Sec14-like PITP is cleanly uncoupled from its canonical in vitro PtdIns-transfer activity and challenge popular functional assumptions regarding lipid-transfer protein involvements in MCS function.
AB - The yeast phosphatidylserine (PtdSer) decarboxylase Psd2 is proposed to engage in a membrane contact site (MCS) for PtdSer decarboxylation to phosphatidylethanolamine (PtdEtn). This proposed MCS harbors Psd2, the Sec14-like phosphatidylinositol transfer protein (PITP) Sfh4, the Stt4 phosphatidylinositol (Ptdlns) 4-OH kinase, the Scs2 tether, and an uncharacterized protein. We report that, of these components, only Sfh4 and Stt4 regulate Psd2 activity in vivo. They do so via distinct mechanisms. Sfh4 operates via a mechanism for which its Ptdlns-transfer activity is dispensable but requires an Sfh4-Psd2 physical interaction. The other requires Stt4-mediated production of Ptdlns-4-phosphate (PtdIns4P), where Stt4 (along with the Sad PtdIns4P phosphatase and endoplasmic reticulum-plasma membrane tethers) indirectly modulate Psd2 activity via a PtdIns4P homeostatic mechanism that influences PtdSer accessibility to Psd2. These results identify an example in which the biological function of a Sec14-like PITP is cleanly uncoupled from its canonical in vitro PtdIns-transfer activity and challenge popular functional assumptions regarding lipid-transfer protein involvements in MCS function.
U2 - 10.1083/jcb.201907128
DO - 10.1083/jcb.201907128
M3 - مقالة
SN - 0021-9525
VL - 219
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
M1 - 201907128
ER -