The Saccharomyces cerevisiae phosphatidylinositol-transfer protein effects a ligand-dependent inhibition of choline-phosphate cytidylyltransferase activity.
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The Saccharomyces cerevisiae protein SEC14p is required for Golgi function and cell viability in vivo. This requirement is obviated by mutations that specifically inactivate the CDP-choline pathway for phosphatidylcholine biosynthesis. The biochemical basis for the in vivo relationship between SEC14p function and the CDP-choline pathway has remained obscure. We now report that SEC14p effects an in vivo depression of CDP-choline pathway activity by inhibiting choline-phosphate cytidylyltransferase (CCTase; EC 188.8.131.52), the rate-determining enzyme of the CDP-choline pathway. Moreover, this SEC14p-mediated inhibition of CCTase was recapitulated in vitro and was saturable. Finally, whereas the SEC14p-dependent inhibition of CCTase in vitro was markedly reduced under assay conditions that were expected to increase levels of phosphatidylinositol-bound SEC14p, assay conditions expected to increase levels of phosphatidylcholine-bound SEC14p resulted in significant potentiation of CCTase inhibition. The collective data suggest that the phosphatidylcholine-bound form of SEC14p effects an essential repression of CDP-choline pathway activity in Golgi membranes by inhibiting CCTase and that the phospholipid-binding/exchange activity of SEC14p represents a mechanism by which the regulatory activity of SEC14p is itself controlled.
author list (cited authors)
Skinner, H. B., McGee, T. P., McMaster, C. R., Fry, M. R., Bell, R. M., & Bankaitis, V. A.
complete list of authors
Skinner, HB||McGee, TP||McMaster, CR||Fry, MR||Bell, RM||Bankaitis, VA