Secretory vesicle budding from the trans-Golgi network is mediated by phosphatidic acid levels.
Phospholipid metabolism plays a central role in regulating vesicular traffic in the secretory pathway. In mammalian cells, activation of a Golgi-associated phospholipase D activity by ADP-ribosylation factor results in hydrolysis of phosphatidylcholine to phosphatidic acid (PA). This reaction has been proposed to stimulate nascent secretory vesicle budding from the trans-Golgi network. It is unclear whether PA itself or diacylglycerol (DAG), a metabolite implicated in yeast secretory vesicle formation, regulates budding. To distinguish between these possibilities we have used a permeabilized cell system supplemented with phospholipid-modifying enzymes that generate either DAG or PA. The data demonstrate that in mammalian cells accumulation of PA rather than DAG is a key step in regulating budding of secretory vesicles from the trans-Golgi network.
Siddhanta
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Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Shields
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D000818:Animals; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism*; D019852:Diacylglycerol Kinase / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010739:Phospholipase D / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism
D004075:Diglycerides; D010712:Phosphatidic Acids; D019269:Phosphatidylinositol 4,5-Diphosphate; D019852:Diacylglycerol Kinase; D010738:Type C Phospholipases; D010739:Phospholipase D; D043265:Phosphatidylinositol Diacylglycerol-Lyase