Phosphatidylinositol 4-kinase IIIβ regulates the transport of ceramide between the endoplasmic reticulum and Golgi

Balázs Tóth, Andras Balla, Hui Ma, Zachary A. Knight, Kevan M. Shokat, Tamas Balla

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The recently identified ceramide transfer protein, CERT, is responsible for the bulk of ceramide transport from the endoplasmic reticulum (ER) to the Golgi. CERT has a C-terminal START domain for ceramide binding and an N-terminal pleckstrin homology domain that binds phosphatidylinositol 4-phosphate suggesting that phosphatidylinositol (PI) 4-kinases are involved in the regulation of CERT-mediated ceramide transport. In the present study fluorescent analogues were used to follow the ER to Golgi transport of ceramide to determine which of the four mammalian PI 4-kinases are involved in this process. Overexpression of pleckstrin homology domains that bind phosphatidylinositol 4-phosphate strongly inhibited the transport of C5-BODIPY-ceramide to the Golgi. A newly identified PI 3-kinase inhibitor, PIK93 that selectively inhibits the type III PI 4-kinase β enzyme, and small interfering RNA-mediated down-regulation of the individual PI 4-kinase enzymes, revealed that PI 4-kinase β has a dominant role in ceramide transport between the ER and Golgi. Accordingly, inhibition of PI 4-kinase III β either by wortmannin or PIK93 inhibited the conversion of [3H]serine-labeled endogenous ceramide to sphingomyelin. Therefore, PI 4-kinase β is a key enzyme in the control of spingomyelin synthesis by controlling the flow of ceramide from the ER to the Golgi compartment.

Original languageEnglish
Pages (from-to)36369-36377
Number of pages9
JournalJournal of Biological Chemistry
Issue number47
Publication statusPublished - Nov 24 2006


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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