Phosphatidylinositol 4-Kinase IIIβ Regulates the Transport of Ceramide between the Endoplasmic Reticulum and Golgi*
By B. Tóth, A. Balla, Hui Ma, Zachary A. Knight, Kevan M. Shokat, T. Balla. Journal of Biological Chemistry, 2006
131 citations recorded by the source corpus.
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 pleck-strin 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.
Subfields: Cell Biology, Physiology, Surgery
View Paper: https://www.semanticscholar.org/paper/d022e80f0493b29a9e2a0250e8d1efdfadec99d9
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Citations in the corpus
- Viral Reorganization of the Secretory Pathway Generates Distinct Organelles for RNA Replication (2010, unknown): “We utilized GFP-tagged FAPP1-PH proteins, which are known to bind PI4P lipid-containing membranes in the presence of Arf1 (Godi et al., 2004; Tóth et al., 2006).”
- Phosphoinositides: tiny lipids with giant impact on cell regulation. (2013, background): “Undoubtedly, type II enzymes are also present in the PM, either under unstimulated conditions (PI4K2A) or after stimulation with PDGF (PI4K2B) (1690).”