Sphingomyelin de novo synthesis pathway.

Intact sphingomyelin biosynthetic pathway is ..

the sphingomyelin/ceramide pathway and DNA synthesis.

AB - Cells genetically deficient in sphingomyelin synthase-1 (SGMS1) or blocked in their synthesis pharmacologically through exposure to a serine palmitoyltransferase inhibitor (myriocin) show strongly reduced surface display of influenza virus glycoproteins hemag-glutinin (HA) and neuraminidase (NA). The transport of HA to the cell surface was assessed by accessibility of HA on intact cells to exogenously added trypsin and to HA-specific antibodies. Rates of de novo synthesis of viral proteins in wild-type and SGMS1-deficient cells were equivalent, and HA negotiated the intracellular trafficking pathway through the Golgi normally. We engineered a strain of influenza virus to allow site-specific labeling of HA and NA using sortase. Accessibility of both HA and NA to sortase was blocked in SGMS1-deficient cells and in cells exposed to myriocin, with a corresponding inhibition of the release of virus particles from infected cells. Generation of influenza virus particles thus critically relies on a functional sphingomyelin biosynthetic pathway, required to drive influenza viral glycoproteins into lipid domains of a composition compatible with virus budding and release.

The increase in the synthetic pathway in the plasmamembrane-enriched fraction was sufficient to account for the measuredincrease in sphingomyelin.

Pathways for ceramide synthesis

Cannabinoids, the active components of Cannabis sativa (marijuana) and their endogenous counterparts, exert their effects by binding to specific G-protein-coupled receptors that modulate adenylyl cyclase and ion channels. Recent research has shown that the CB1 cannabinoid receptor is also coupled to the generation of the lipid second messenger ceramide via two different pathways: sphingomyelin hydrolysis and ceramide synthesis de novo. Sustained ceramide accumulation in tumor cells mediates cannabinoid-induced apoptosis, as evidenced by in vitro and in vivo studies. This effect seems to be due to the impact of ceramide on key cell signalling systems such as the extracellular signal-regulated kinase cascade and the Akt pathway. These findings provide a new conceptual view on how cannabinoids act, and raise interesting physiological and therapeutic questions.

TY - JOUR. T1 - Intact sphingomyelin biosynthetic pathway is essential for intracellular transport of influenza virus glycoproteins. AU - Tafesse,Fikadu G.

N2 - Cells genetically deficient in sphingomyelin synthase-1 (SGMS1) or blocked in their synthesis pharmacologically through exposure to a serine palmitoyltransferase inhibitor (myriocin) show strongly reduced surface display of influenza virus glycoproteins hemag-glutinin (HA) and neuraminidase (NA). The transport of HA to the cell surface was assessed by accessibility of HA on intact cells to exogenously added trypsin and to HA-specific antibodies. Rates of de novo synthesis of viral proteins in wild-type and SGMS1-deficient cells were equivalent, and HA negotiated the intracellular trafficking pathway through the Golgi normally. We engineered a strain of influenza virus to allow site-specific labeling of HA and NA using sortase. Accessibility of both HA and NA to sortase was blocked in SGMS1-deficient cells and in cells exposed to myriocin, with a corresponding inhibition of the release of virus particles from infected cells. Generation of influenza virus particles thus critically relies on a functional sphingomyelin biosynthetic pathway, required to drive influenza viral glycoproteins into lipid domains of a composition compatible with virus budding and release.

19/12/2017 · Synthesis of surface sphingomyelin in the plasma membrane recycling pathway of BHK Cells


Choline | Linus Pauling Institute | Oregon State University

Constitutive degradation of sphingolipids and glycosphingolipidstakes place in the acidic subcellular compartments, the lateendosomes and the . In case of glycosphingolipids,exohydrolases, acting at acidic pH optima, cause the stepwiserelease of monosaccharide units from the end of the oligosaccharidechains one after the other leading to the generation of ceramidewhereas sphingomyelin is converted to ceramide by acid . Ceramide can be furtherhydrolyzed by acid ceramidase to form sphingosine and a free fattyacid, both of which are able to leave the lysosome in contrast toceramide. The long-chain sphingoid bases released from the lysosomemay then re-enter pathways for synthesis of ceramide and/or . Thesalvage pathway re-utilizes long-chain sphingoid bases to formceramide through the action of ceramide synthase. Thus, family members probablytrap free sphingosine released from the lysosome at the surface ofthe or inendoplasmic reticulum-associated membranes. It should also be notedthat the salvage pathway has been estimated to contribute from 50%to 90% of sphingolipid biosynthesis

Anthracycline Chemotherapy Agents

Cells genetically deficient in sphingomyelin synthase-1 (SGMS1) or blocked in their synthesis pharmacologically through exposure to a serine palmitoyltransferase inhibitor (myriocin) show strongly reduced surface display of influenza virus glycoproteins hemag-glutinin (HA) and neuraminidase (NA). The transport of HA to the cell surface was assessed by accessibility of HA on intact cells to exogenously added trypsin and to HA-specific antibodies. Rates of de novo synthesis of viral proteins in wild-type and SGMS1-deficient cells were equivalent, and HA negotiated the intracellular trafficking pathway through the Golgi normally. We engineered a strain of influenza virus to allow site-specific labeling of HA and NA using sortase. Accessibility of both HA and NA to sortase was blocked in SGMS1-deficient cells and in cells exposed to myriocin, with a corresponding inhibition of the release of virus particles from infected cells. Generation of influenza virus particles thus critically relies on a functional sphingomyelin biosynthetic pathway, required to drive influenza viral glycoproteins into lipid domains of a composition compatible with virus budding and release.