CERT and intracellular trafficking of ceramide

Hanada, Kentaro; Kumagai, Keigo; Tomishige, Nario; Kawano, Miyuki

doi:10.1016/j.bbalip.2007.01.009

Cited by 134 publications

(100 citation statements)

References 90 publications

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“…Alternatively, ATP may allow the recycling of CERT after its binding to PI4P or VAP or it could energize an ATP-dependent translocase that moves ceramide from the cytosolic side of the Golgi to the luminal side where the catalytic domain of SMS is located. 36 The spatial organization of the CERT-mediated transfer of ceramide between the ER and Golgi is not clear. The over-expression of a green fluorescent protein (GFP) tagged-CERT in CHO cells showed its localization at the cis/medial Golgi apparatus pointing to the early Golgi as the site for ceramide transfer.…”

Section: Discovery Of a Ceramide Transfer Protein With A Key Role In mentioning

confidence: 99%

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

Holthuis

Luberto

2010

Advances in Experimental Medicine and Biology

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In the last five years tremendous progress has been made toward the understanding of the mechanisms that govern sphingomyelin (SM) synthesis in animal cells. In line with the complexity of most biological processes, also in the case of SM biosynthesis, the more we learn the more enigmatic and finely tuned the system appears. Therefore with this review we aim first, at highlighting the most significant discoveries that advanced our knowledge and understanding of SM biosynthesis, starting from the discovery of SM to the identification of the enzymes responsible for its production; and second, at discussing old and new riddles that such discoveries pose to current investigators.

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Section: Discovery Of a Ceramide Transfer Protein With A Key Role In mentioning

confidence: 99%

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

Holthuis

Luberto

2010

Advances in Experimental Medicine and Biology

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“…4), which have revealed some of the protein machinery involved in this process. Through genetic and biochemical approaches, the Cer transport protein (Cert) was identified as an essential component for the trafficking of Cer from its site of synthesis in the ER to the site of its conversion to sphingomyelin in the Golgi (36).…”

Section: Psd2-nt-hismentioning

confidence: 99%

“…Previous work from our laboratory has identified a number of proteins and lipid motifs necessary in vivo and in (2); scs2⌬ mutant and wild-type Stt4p (3); and wild-type Scs2 and Stt4pFFAT mutant (4). C and D, Etn auxotrophy assays to determine the functionality of the PstB transport event in the experimental constructs outlined in B.…”

Section: Psd2-nt-hismentioning

confidence: 99%

“…Psd2p is a membrane-associated enzyme, and because previous attempts at expression and manipulation of subdomains of this protein in soluble form have failed, 4 we took a different approach to generating a soluble fragment with which to interrogate the protein and lipid interactions of Psd2p. An updated analysis of the Psd2p sequence with the Pfam conserved domain database (23) revealed a second, highly divergent C2 domain at the extreme N terminus, which had not been identified in previous studies by our laboratory (8,17).…”

Section: Recombinant Pstb2pmentioning

confidence: 99%

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An Assembly of Proteins and Lipid Domains Regulates Transport of Phosphatidylserine to Phosphatidylserine Decarboxylase 2 in Saccharomyces cerevisiae

Riekhof

Jones

et al. 2014

Journal of Biological Chemistry

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Background:The machinery for interorganelle phosphatidylserine (PtdSer) transport is poorly defined at the molecular level. Results: Molecular interaction studies identify specific protein-protein and protein-lipid interactions in PtdSer transport. Conclusion: A protein and lipid interaction network defines key participants in PS transport to the locus of PtdSer-decarboxylase 2. Significance: This study identifies important molecular participants involved in non-vesicular phospholipid traffic.

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“…These three LT/BPs, which shuttle between the cytosol and the Golgi complex, are potentially functionally interdependent: CERT transports ceramide from the ER to the Golgi, and ceramide and PC are converted into sphingomyelin (SM) and diacylglycerol (DAG) by SM synthase (SMS) in the trans-Golgi (Hanada et al, 2007). Nir2 is a phosphatidylinositol/phosphatidylcholine (PI/PC)-transfer protein that is involved in the regulation of DAG levels at the Golgi apparatus through inhibition of the CDP-choline pathway for PC biosynthesis (Litvak et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Coordinated Lipid Transfer between the Endoplasmic Reticulum and the Golgi Complex Requires the VAP Proteins and Is Essential for Golgi-mediated Transport

Peretti

Dahan

Shimoni

et al. 2008

MBoC

290

272

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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 Golgimediated transport events. These effects are coordinately mediated by the lipid-transfer/binding proteins Nir2, oxysterolbinding 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. INTRODUCTIONThe unique lipid compositions of the secretory and endocytic organelles are critical for maintaining their distinct structural and functional identities (van Meer, 2000). Their identities are maintained despite extensive interconnecting vesicular-trafficking pathways, and they require tight regulation of lipid sorting, metabolism, and transport (van Meer, 1993;Pomorski et al., 2001;van Meer and Sprong, 2004). Increasing lines of evidence suggest that lipid-transfer proteins (LTPs) play a major role in regulating the lipid composition of membranous organelles (Sprong et al., 2001;De Matteis et al., 2007). These proteins facilitate lipid transfer between a donor and acceptor membrane (Holthuis and Levine, 2005), and they usually contain dual-targeting determinants for different membrane compartments. LTPs have been proposed to efficiently transfer lipids at membrane contact sites (MCSs) (Holthuis and Levine, 2005;Levine and Loewen, 2006).MCSs or zones of close apposition between the ER membranes and other cellular membranes, including the plasma membrane (PM), the membranes of the vacuoles, mitochondria, peroxisomes, lipid droplets, late endosomes, lysosomes, and the Golgi apparatus, have been identified in all eukaryotes by morphological and biochemical studies (Shore and Tata, 1977;Levine, 2004;Levine and Loewen, 2006). More recently, electron tomography studies have identified close contacts (10 -20 nm) between the ER and the outer mitochondrial membrane (Perkins et al., 1997) and between a specialized trans-ER and the three trans-most cisternae of the Golgi complex (Ladinsky et al., 1999;Marsh et al., 2001Marsh et al., , 2004. This ...

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CERT and intracellular trafficking of ceramide

Cited by 134 publications

References 90 publications

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family

An Assembly of Proteins and Lipid Domains Regulates Transport of Phosphatidylserine to Phosphatidylserine Decarboxylase 2 in Saccharomyces cerevisiae

Coordinated Lipid Transfer between the Endoplasmic Reticulum and the Golgi Complex Requires the VAP Proteins and Is Essential for Golgi-mediated Transport

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