Maintenance of the diacylglycerol level in the Golgi apparatus by the Nir2 protein is critical for Golgi secretory function

Abstract

The level of diacylglycerol (DAG) in the Golgi apparatus is crucial for protein transport to the plasma membrane. Studies in budding yeast indicate that Sec14p, a phosphatidylinositol (PI)-transfer protein, is involved in regulating DAG homeostasis in the Golgi complex. Here, we show that Nir2, a peripheral Golgi protein containing a PI-transfer domain, is essential for maintaining the structural and functional integrity of the Golgi apparatus in mammalian cells. Depletion of Nir2 by RNAi leads to substantial inhibition of protein transport from the trans-Golgi network to the plasma membrane, and causes a reduction in the DAG level in the Golgi apparatus. Remarkably, inactivation of cytidine [corrected] 5'-diphosphate (CDP)-choline pathway for phosphatidylcholine biosynthesis restores both effects. These results indicate that Nir2 is involved in maintaining a critical DAG pool in the Golgi apparatus by regulating its consumption via the CDP-choline pathway, demonstrating the interface between secretion from the Golgi and lipid homeostasis.

Protein kinase D1/2 is involved in the maturation of multivesicular bodies and secretion of exosomes in T and B lymphocytes

“…DAG-mediated PKD activation regulates vesicle budding and fission from the TGN, a process negatively regulated by DGK. 16,19,65 Our results here identify an additional PKD1/2 function as a major downstream effector of DGKα in the control of MVB traffic and exosome secretion in T and B cells. DGKα-mediated DAG consumption limits PKD subcellular location and activation in T ymphocytes during IS formation.…”

“…[10][11][12][13][14][15] The discovery of exosome involvement in these responses increased interest in the regulation of exosome biogenesis and secretory traffic, with special attention to the contribution of lipids such as ceramide and DAG, as well as DAG-binding proteins. 14,[16][17][18][19][20][21] These studies suggest that positive and negative DAG regulators may control secretory traffic. By transforming DAG into phosphatidic acid (PA), diacylglycerol kinase α (DGKα) is essential for the negative control of DAG function in T lymphocytes.…”

“…23,24 The secretory vesicle pathway involves several DAGcontrolled checkpoints at which DGKα may act; these include vesicle formation and fission at the trans-Golgi network (TGN), MVB maturation, as well as their transport, docking and fusion to the plasma membrane. 9,[16][17][18][19][20] The molecular components that regulate some of these trafficking processes include protein kinase D (PKD) family members. 21 PKD1 activity, for instance, regulates fission of transport vesicles from TGN via direct interaction with the pre-existing DAG pool at this site.…”

Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice

“…The corresponding proteins have an important role in phospholipid biosynthesis. 38 Some of these changes are expected to have an effect on the synthesis of HDL. 39 Effect of fenofibrate on genes affecting triglyceride hydrolysis, FA transport, b-oxidation, other mitochondrial function, fatty acid biosynthesis and carbohydrate metabolism The monoglycerides generated by the actions of Lpl and Pnliprp, which are upregulated, can be channeled toward phospholipid biosynthesis.…”

“…Finally, the overexpression of Chka will promote phosphocholine biosynthesis and the overexpression of Pitpnm1, which regulates DAG consumption via the CDP-choline pathway, may promote phosphatidylcholine biosynthesis. 38 A previous study showed that the biosynthesis of phosphatidylcholine in the liver is important for HDL formation. 39 Overall, the upregulation of the genes involved in phospholipid biosynthesis as well as that of Lpl may account for the observed increase in HDL levels, and the modest downregulation of the Srb1 gene may account for the increase in the size of HDL in response to fenofibrate treatment.…”