title: 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.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Litvak
authors.forename: Nili
authors.initials: N
authors.lastname: Dahan
authors.forename: Sreekumar
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Helena
authors.initials: H
authors.lastname: Sabanay
authors.forename: Sima
authors.initials: S
authors.lastname: Lev
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002794:Choline; D002855:Chromatography, Thin Layer; D003596:Cytosine / Q000737:chemistry; D004075:Diglycerides / Q000378:metabolism*; D011756:Diphosphates / Q000737:chemistry; D005136:Eye Proteins / Q000378:metabolism / Q000502:physiology*; D006025:Glycosaminoglycans / Q000737:chemistry; D006056:Golgi Apparatus / Q000378:metabolism* / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D010713:Phosphatidylcholines / Q000737:chemistry; D049294:Phospholipid Transfer Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D004718:Saccharomycetales; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004075:Diglycerides; D011756:Diphosphates; D005136:Eye Proteins; C028391:G protein, vesicular stomatitis virus; D006025:Glycosaminoglycans; D008055:Lipids; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C113505:PITPNM1 protein, human; D010713:Phosphatidylcholines; D049294:Phospholipid Transfer Proteins; C483438:SEC14 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014759:Viral Envelope Proteins; D003596:Cytosine; D002794:Choline