title: Coordinated lipid transfer between the endoplasmic reticulum and the Golgi complex requires the VAP proteins and is essential for Golgi-mediated transport.
abstract: Lipid transport between intracellular organelles is mediated by vesicular and nonvesicular transport mechanisms and is critical for maintaining the identities of different cellular membranes. Nonvesicular lipid transport between the endoplasmic reticulum (ER) and the Golgi complex has been proposed to affect the lipid composition of the Golgi membranes. Here, we show that the integral ER-membrane proteins VAP-A and VAP-B affect the structural and functional integrity of the Golgi complex. Depletion of VAPs by RNA interference reduces the levels of phosphatidylinositol-4-phosphate (PI4P), diacylglycerol, and sphingomyelin in the Golgi membranes, and it leads to substantial inhibition of Golgi-mediated transport events. These effects are coordinately mediated by the lipid-transfer/binding proteins Nir2, oxysterol-binding protein (OSBP), and ceramide-transfer protein (CERT), which interact with VAPs via their FFAT motif. The effect of VAPs on PI4P levels is mediated by the phosphatidylinositol/phosphatidylcholine transfer protein Nir2, which is required for Golgi targeting of OSBP and CERT and the subsequent production of diacylglycerol and sphingomyelin. We propose that Nir2, OSBP, and CERT function coordinately at the ER-Golgi membrane contact sites, thereby affecting the lipid composition of the Golgi membranes and consequently their structural and functional identities.
authors.affiliation: The Molecular Cell Biology Department, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Diego
authors.initials: D
authors.lastname: Peretti
authors.forename: Nili
authors.initials: N
authors.lastname: Dahan
authors.forename: Eyal
authors.initials: E
authors.lastname: Shimoni
authors.forename: Koret
authors.initials: K
authors.lastname: Hirschberg
authors.forename: Sima
authors.initials: S
authors.lastname: Lev
mesh_terms: D020816:Amino Acid Motifs; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005136:Eye Proteins / Q000737:chemistry / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011987:Receptors, Steroid / Q000737:chemistry / Q000378:metabolism*; D013109:Sphingomyelins / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D000098825:Oxysterol Binding Proteins
chemical_list: D002135:Calcium-Binding Proteins; D005136:Eye Proteins; D008055:Lipids; D008565:Membrane Proteins; C113505:PITPNM1 protein, human; D018129:Phosphatidylinositol Phosphates; D011987:Receptors, Steroid; D013109:Sphingomyelins; C114051:VAPA protein, human; C496748:VAPB protein, human; D033921:Vesicular Transport Proteins; D000098825:Oxysterol Binding Proteins; C119090:CERT1 protein, human; D017346:Protein Serine-Threonine Kinases