title: PKD regulates membrane fission to generate TGN to cell surface transport carriers.
abstract: The serine/threonine protein kinase D (PKD) is recruited to the trans-Golgi network (TGN) by binding diacylglycerol (DAG) and the ARF1 GTPase. PKD, at the TGN, promotes the production of phosphatidylinositol-4 phosphate (PI4P) by activating the lipid kinase phophatidylinositol 4-kinase IIIß (PI4KIIIß). PI4P recruits proteins such as oxysterol-binding protein 1 (OSBP) and ceramide transport protein (CERT) that control sphingolipid and sterol levels at the TGN. CERT mediated transport of ceramide to the TGN, we suggest, is used for increasing the local production and concentration of DAG. Once the crucial concentration of DAG is achieved, OSBP and CERT dissociate from the TGN on phosphorylation by PKD and DAG is sequentially converted into phosphatidic acid (PA) and lyso-PA (LPA). Therefore, the net effect of the activated PKD at the TGN is the sequential production of the modified lipids DAG, PA, and LPA that are necessary for membrane fission to generate cell surface specific transport carriers.
authors.affiliation: Center for Genomic Regulation, Dr. Aiguader 88, Barcelona, Spain. vivek.malhotra@crg.es
authors.forename: Vivek
authors.initials: V
authors.lastname: Malhotra
authors.forename: Felix
authors.initials: F
authors.lastname: Campelo
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D004075:Diglycerides / Q000096:biosynthesis*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis*; D008566:Membranes / Q000378:metabolism*; D008954:Models, Biological; D018129:Phosphatidylinositol Phosphates; D011493:Protein Kinase C / Q000378:metabolism*; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D004075:Diglycerides; D008565:Membrane Proteins; D018129:Phosphatidylinositol Phosphates; C037178:phosphatidylinositol 4-phosphate; C089212:protein kinase D; D011493:Protein Kinase C; D020823:ADP-Ribosylation Factor 1