title: Apoptosis and signalling in acid sphingomyelinase deficient cells.
abstract: BACKGROUND
  Recent evidence suggests that the activation of a non-specific lipid scramblase during apoptosis induces the flipping of sphingomyelin from the cell surface to the cytoplasmic leaftet of the plasma membrane. Inner leaflet sphingomyelin is then cleaved to ceramide by a neutral sphingomyelinase. The production of this non-membrane forming lipid induces blebbing of the plasma membrane to aid rapid engulfment by professional phagocytes. However contrary evidence suggests that cells which are deficient in acid sphingomyelinase are defective in apoptosis signalling. This data has been interpreted as support for the activation of acid sphingomyelinase as an early signal in apoptosis.
  
  
  OBJECTIVE
  An alternative explanation is put forward whereby the accumulation of intracellular sphingomyelin in sphingomyelinase deficient cells leads to the formation of intracellular rafts which lead to the sequestration of important signalling molecules that are normally present on the cell surface where they perform their function.
  
  
  METHODS
  It is expected that the subcellular distribution of important signalling molecules is altered in acid sphingomyelinase deficient cells, leading to their sequestration in late endosomes/lysosomes. Other sphingolipid storage diseases such as Niemann-Pick type C which have normal acid sphingomyelinase activity would also be expected to show the same phenotype.
  
  
  CONCLUSIONS
  If true the hypothesis would provide a mechanism for the pathology of the sphingolipid storage diseases at the cellular level and also have implications for the role of ceramide in apoptosis.
authors.affiliation: Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. dan@glycob.ox.ac.uk
authors.forename: D J
authors.initials: DJ
authors.lastname: Sillence
mesh_terms: D000818:Animals; D017209:Apoptosis; D008247:Lysosomes / Q000737:chemistry; D021962:Membrane Microdomains / Q000737:chemistry; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*; D013109:Sphingomyelins / Q000032:analysis
chemical_list: D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase