Functional anatomy of phospholipid binding and regulation of phosphoinositide homeostasis by proteins of the sec14 superfamily. Academic Article uri icon

abstract

  • Sec14, the major yeast phosphatidylinositol (PtdIns)/phosphatidylcholine (PtdCho) transfer protein, regulates essential interfaces between lipid metabolism and membrane trafficking from the trans-Golgi network (TGN). How Sec14 does so remains unclear. We report that Sec14 binds PtdIns and PtdCho at distinct (but overlapping) sites, and both PtdIns- and PtdCho-binding activities are essential Sec14 activities. We further show both activities must reside within the same molecule to reconstitute a functional Sec14 and for effective Sec14-mediated regulation of phosphoinositide homeostasis in vivo. This regulation is uncoupled from PtdIns-transfer activity and argues for an interfacial presentation mode for Sec14-mediated potentiation of PtdIns kinases. Such a regulatory role for Sec14 is a primary counter to action of the Kes1 sterol-binding protein that antagonizes PtdIns 4-OH kinase activity in vivo. Collectively, these findings outline functional mechanisms for the Sec14 superfamily and reveal additional layers of complexity for regulating phosphoinositide homeostasis in eukaryotes.

published proceedings

  • Mol Cell

altmetric score

  • 1

author list (cited authors)

  • Schaaf, G., Ortlund, E. A., Tyeryar, K. R., Mousley, C. J., Ile, K. E., Garrett, T. A., ... Bankaitis, V. A.

citation count

  • 188

complete list of authors

  • Schaaf, Gabriel||Ortlund, Eric A||Tyeryar, Kimberly R||Mousley, Carl J||Ile, Kristina E||Garrett, Teresa A||Ren, Jihui||Woolls, Melissa J||Raetz, Christian RH||Redinbo, Matthew R||Bankaitis, Vytas A

publication date

  • January 1, 2008 11:11 AM