title: Acute perturbations in Golgi organization impact de novo sphingomyelin synthesis.
abstract: The mammalian Golgi apparatus is composed of multiple stacks of cisternal membranes organized laterally into a ribbon-like structure, with close apposition of trans Golgi regions with specialized endoplasmic reticulum (ER) membranes. These contacts may be the site of ceramide transfer from its site of synthesis (ER) to sphingomyelin (SM) synthase through ceramide transfer protein (CERT). CERT extracts ceramide from the ER and transfers it to Golgi membranes but the role of overall Golgi structure in this process is unknown. We show here that localization of CERT in puncta around the Golgi complex requires both ER- and Golgi-binding domains of CERT. To examine how Golgi structure contributes to SM synthesis, we treated cells with Golgi-perturbing drugs and measured newly synthesized SM. Interestingly, disruption of Golgi morphology with nocodazole, but not ilimaquinone inhibited SM synthesis. Decreased localization of CERT with a Golgi marker correlated with decreased SM synthesis. We propose that some Golgi structural perturbations interfere with efficient ceramide trafficking through CERT, and thus SM synthesis. The organization of the mammalian Golgi ribbon together with CERT may promote specific ER-Golgi interactions for efficient delivery of ceramide for SM synthesis.
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Suchismita
authors.initials: S
authors.lastname: Chandran
authors.forename: Carolyn E
authors.initials: CE
authors.lastname: Machamer
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013109:Sphingomyelins / Q000096:biosynthesis*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000378:metabolism
chemical_list: D017931:DNA Primers; D013109:Sphingomyelins; C119090:CERT1 protein, human; D017346:Protein Serine-Threonine Kinases; D017855:Transferases (Other Substituted Phosphate Groups); C070186:phosphatidylcholine-ceramide phosphocholine transferase; D015739:Nocodazole
references.citation: Trends Cell Biol. 2005 Jun;15(6):312-8
references.pmid: 15953549
references.citation: J Cell Biol. 1999 Mar 22;144(6):1135-49
references.pmid: 10087259
references.citation: Cell. 1993 Jun 18;73(6):1079-90
references.pmid: 8513494
references.citation: Trends Cell Biol. 1998 Jan;8(1):2-10
references.pmid: 9695800
references.citation: Biochem J. 1993 Jan 1;289 ( Pt 1):307-12
references.pmid: 8424768
references.citation: Nat Rev Mol Cell Biol. 2005 Mar;6(3):209-20
references.pmid: 15738987
references.citation: J Cell Biol. 2007 Jul 2;178(1):15-22
references.pmid: 17591919
references.citation: Biochim Biophys Acta. 1993 Feb 23;1146(1):9-16
references.pmid: 8443228
references.citation: J Biol Chem. 2008 Mar 7;283(10):6584-93
references.pmid: 18165232
references.citation: Mol Biol Cell. 2006 Jun;17(6):2604-16
references.pmid: 16571669
references.citation: Exp Cell Res. 2004 Jan 15;292(2):385-92
references.pmid: 14697345
references.citation: J Biol Chem. 1992 Mar 15;267(8):5052-5
references.pmid: 1544889
references.citation: J Cell Biol. 2007 Oct 8;179(1):101-15
references.pmid: 17923531
references.citation: Nat Cell Biol. 2004 May;6(5):393-404
references.pmid: 15107860
references.citation: Can J Biochem Physiol. 1959 Aug;37(8):911-7
references.pmid: 13671378
references.citation: Mol Cell Biochem. 2006 Jun;286(1-2):23-31
references.pmid: 16601923
references.citation: Cell. 1989 Mar 10;56(5):801-13
references.pmid: 2647301
references.citation: J Biol Chem. 2006 Oct 6;281(40):30279-88
references.pmid: 16895911
references.citation: J Biol Chem. 2002 Sep 27;277(39):35833-9
references.pmid: 12130652
references.citation: J Biol Chem. 2007 Jun 15;282(24):17758-66
references.pmid: 17442665
references.citation: Biochem J. 1998 Aug 1;333 ( Pt 3):779-86
references.pmid: 9677340
references.citation: Biochim Biophys Acta. 2007 Jun;1771(6):644-53
references.pmid: 17314061
references.citation: J Biol Chem. 1992 Jun 25;267(18):12443-51
references.pmid: 1618752
references.citation: FEBS Lett. 2000 Jul 28;478(1-2):9-12
references.pmid: 10922460
references.citation: J Cell Biol. 1993 Sep;122(6):1197-206
references.pmid: 8104190
references.citation: Cell Mol Life Sci. 2001 Dec;58(14):2053-68
references.pmid: 11814056
references.citation: Nature. 2003 Dec 18;426(6968):803-9
references.pmid: 14685229
references.citation: J Biol Chem. 1992 Dec 5;267(34):24906-11
references.pmid: 1447226
references.citation: Mech Ageing Dev. 2001 Jul 15;122(9):895-908
references.pmid: 11348657
references.citation: Mol Biol Cell. 1996 Apr;7(4):631-50
references.pmid: 8730104
references.citation: Nature. 2007 Sep 6;449(7158):62-7
references.pmid: 17687330
references.citation: J Microsc. 1993 Mar;169(3):375-382
references.pmid: 33930978