Acid Sphingomyelinase Activity is Regulated by Membrane Lipids and Facilitates Cholesterol Transfer by NPC2

Overview

Journal J Lipid Res

Publisher Elsevier

Specialty Biochemistry

Date 2014 Oct 24

PMID 25339683

Citations 34

Authors

Vincent O Oninla

Bernadette Breiden

Jonathan O Babalola

Konrad Sandhoff

Affiliations

Soon will be listed here.

Abstract

During endocytosis, membrane components move to intraluminal vesicles of the endolysosomal compartment for digestion. At the late endosomes, cholesterol is sorted out mainly by two sterol-binding proteins, Niemann-Pick protein type C (NPC)1 and NPC2. To study the NPC2-mediated intervesicular cholesterol transfer, we developed a liposomal assay system. (Abdul-Hammed, M., B. Breiden, M. A. Adebayo, J. O. Babalola, G. Schwarzmann, and K. Sandhoff. 2010. Role of endosomal membrane lipids and NPC2 in cholesterol transfer and membrane fusion. J. Lipid Res. 51: 1747-1760.) Anionic lipids stimulate cholesterol transfer between liposomes while SM inhibits it, even in the presence of anionic bis(monoacylglycero)phosphate (BMP). Preincubation of vesicles containing SM with acid sphingomyelinase (ASM) (SM phosphodiesterase, EC 3.1.4.12) results in hydrolysis of SM to ceramide (Cer), which enhances cholesterol transfer. Besides SM, ASM also cleaves liposomal phosphatidylcholine. Anionic phospholipids derived from the plasma membrane (phosphatidylglycerol and phosphatidic acid) stimulate SM and phosphatidylcholine hydrolysis by ASM more effectively than BMP, which is generated during endocytosis. ASM-mediated hydrolysis of liposomal SM was also stimulated by incorporation of diacylglycerol (DAG), Cer, and free fatty acids into the liposomal membranes. Conversely, phosphatidylcholine hydrolysis was inhibited by incorporation of cholesterol, Cer, DAG, monoacylglycerol, and fatty acids. Our data suggest that SM degradation by ASM is required for physiological secretion of cholesterol from the late endosomal compartment, and is a key regulator of endolysosomal lipid digestion.

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References

Kolesnick R, Clegg S . 1,2-Diacylglycerols, but not phorbol esters, activate a potential inhibitory pathway for protein kinase C in GH3 pituitary cells. Evidence for involvement of a sphingomyelinase. J Biol Chem. 1988; 263(14):6534-7. View

Kolzer M, Werth N, Sandhoff K . Interactions of acid sphingomyelinase and lipid bilayers in the presence of the tricyclic antidepressant desipramine. FEBS Lett. 2004; 559(1-3):96-8. DOI: 10.1016/S0014-5793(04)00033-X. View

Cornelius F . Modulation of Na,K-ATPase and Na-ATPase activity by phospholipids and cholesterol. I. Steady-state kinetics. Biochemistry. 2001; 40(30):8842-51. DOI: 10.1021/bi010541g. View

Babalola J, Wendeler M, Breiden B, Arenz C, Schwarzmann G, Locatelli-Hoops S . Development of an assay for the intermembrane transfer of cholesterol by Niemann-Pick C2 protein. Biol Chem. 2007; 388(6):617-26. DOI: 10.1515/BC.2007.063. View

Freeman S, Shankaran P, Wolfe L, Callahan J . Phosphatidylcholine and 4-methylumbelliferyl phosphorylcholine hydrolysis by purified placental sphingomyelinase. Can J Biochem Cell Biol. 1985; 63(4):272-7. DOI: 10.1139/o85-040. View

Harzer K, Massenkeil G, Frohlich E . Concurrent increase of cholesterol, sphingomyelin and glucosylceramide in the spleen from non-neurologic Niemann-Pick type C patients but also patients possibly affected with other lipid trafficking disorders. FEBS Lett. 2003; 537(1-3):177-81. DOI: 10.1016/s0014-5793(03)00100-5. View

Yeung T, Gilbert G, Shi J, Silvius J, Kapus A, Grinstein S . Membrane phosphatidylserine regulates surface charge and protein localization. Science. 2008; 319(5860):210-3. DOI: 10.1126/science.1152066. View

Safanda J, Fakan F . Histochemical and biochemical observations of the spleen in atypical Niemann-Pick disease and in idiopathic thrombocytopenic purpura. Acta Histochem. 1981; 68(2):164-75. DOI: 10.1016/S0065-1281(81)80072-4. View

Remmel N, Locatelli-Hoops S, Breiden B, Schwarzmann G, Sandhoff K . Saposin B mobilizes lipids from cholesterol-poor and bis(monoacylglycero)phosphate-rich membranes at acidic pH. Unglycosylated patient variant saposin B lacks lipid-extraction capacity. FEBS J. 2007; 274(13):3405-20. DOI: 10.1111/j.1742-4658.2007.05873.x. View

10.

Friedland N, Liou H, Lobel P, Stock A . Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease. Proc Natl Acad Sci U S A. 2003; 100(5):2512-7. PMC: 151372. DOI: 10.1073/pnas.0437840100. View

11.

Schuchman E, Suchi M, Takahashi T, Sandhoff K, Desnick R . Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs. J Biol Chem. 1991; 266(13):8531-9. View

12.

Mobius W, van Donselaar E, Ohno-Iwashita Y, Shimada Y, Heijnen H, Slot J . Recycling compartments and the internal vesicles of multivesicular bodies harbor most of the cholesterol found in the endocytic pathway. Traffic. 2003; 4(4):222-31. DOI: 10.1034/j.1600-0854.2003.00072.x. View

13.

Karten B, Peake K, Vance J . Mechanisms and consequences of impaired lipid trafficking in Niemann-Pick type C1-deficient mammalian cells. Biochim Biophys Acta. 2009; 1791(7):659-70. DOI: 10.1016/j.bbalip.2009.01.025. View

14.

Kolter T, Sandhoff K . Lysosomal degradation of membrane lipids. FEBS Lett. 2009; 584(9):1700-12. DOI: 10.1016/j.febslet.2009.10.021. View

15.

Schutze S, Potthoff K, Machleidt T, Berkovic D, Wiegmann K, Kronke M . TNF activates NF-kappa B by phosphatidylcholine-specific phospholipase C-induced "acidic" sphingomyelin breakdown. Cell. 1992; 71(5):765-76. DOI: 10.1016/0092-8674(92)90553-o. View

16.

Jenkins R, Idkowiak-Baldys J, Simbari F, Canals D, Roddy P, Riner C . A novel mechanism of lysosomal acid sphingomyelinase maturation: requirement for carboxyl-terminal proteolytic processing. J Biol Chem. 2010; 286(5):3777-88. PMC: 3030379. DOI: 10.1074/jbc.M110.155234. View

17.

Te Vruchte D, Lloyd-Evans E, Veldman R, Neville D, Dwek R, Platt F . Accumulation of glycosphingolipids in Niemann-Pick C disease disrupts endosomal transport. J Biol Chem. 2004; 279(25):26167-75. DOI: 10.1074/jbc.M311591200. View

18.

Rodriguez-Lafrasse C, Rousson R, Pentchev P, Louisot P, Vanier M . Free sphingoid bases in tissues from patients with type C Niemann-Pick disease and other lysosomal storage disorders. Biochim Biophys Acta. 1994; 1226(2):138-44. DOI: 10.1016/0925-4439(94)90021-3. View

19.

Quintern L, Weitz G, Nehrkorn H, Tager J, Schram A, Sandhoff K . Acid sphingomyelinase from human urine: purification and characterization. Biochim Biophys Acta. 1987; 922(3):323-36. DOI: 10.1016/0005-2760(87)90055-5. View

20.

HURWITZ R, Ferlinz K, Vielhaber G, Moczall H, Sandhoff K . Processing of human acid sphingomyelinase in normal and I-cell fibroblasts. J Biol Chem. 1994; 269(7):5440-5. View