Alterations in the properties of the cell membrane due to glycosphingolipid accumulation in a model of Gaucher disease

Sci Rep. 2018 Jan 9;8(1):157. doi: 10.1038/s41598-017-18405-8.


Gaucher disease is a lysosomal storage disease characterized by the malfunction of glucocerebrosidase resulting in the accumulation of glucosylceramide and other sphingolipids in certain cells. Although the disease symptoms are usually attributed to the storage of undigested substrate in lysosomes, here we show that glycosphingolipids accumulating in the plasma membrane cause profound changes in the properties of the membrane. The fluidity of the sphingolipid-enriched membrane decreased accompanied by the enlargement of raft-like ordered membrane domains. The mobility of non-raft proteins and lipids was severely restricted, while raft-resident components were only mildly affected. The rate of endocytosis of transferrin receptor, a non-raft protein, was significantly retarded in Gaucher cells, while the endocytosis of the raft-associated GM1 ganglioside was unaffected. Interferon-γ-induced STAT1 phosphorylation was also significantly inhibited in Gaucher cells. Atomic force microscopy revealed that sphingolipid accumulation was associated with a more compliant membrane capable of producing an increased number of nanotubes. The results imply that glycosphingolipid accumulation in the plasma membrane has significant effects on membrane properties, which may be important in the pathogenesis of Gaucher disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Endocytosis
  • Fluorescent Antibody Technique
  • Gaucher Disease / genetics
  • Gaucher Disease / metabolism*
  • Glucosylceramidase / genetics
  • Glucosylceramidase / metabolism
  • Glycosphingolipids / metabolism*
  • Humans
  • Macrophages / metabolism
  • Membrane Microdomains / metabolism
  • Microscopy, Atomic Force
  • Mutation
  • STAT Transcription Factors / metabolism
  • Signal Transduction
  • Sphingolipids / metabolism
  • Transferrin / metabolism


  • Glycosphingolipids
  • STAT Transcription Factors
  • Sphingolipids
  • Transferrin
  • Glucosylceramidase