GPI anchoring leads to sphingolipid-dependent retention of endocytosed proteins in the recycling endosomal compartment

Samit Chatterjee, Elizabeth R. Smith, Kentaro Hanada, Victoria L. Stevens, Satyajit Mayor

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Glycosylphosphatidylinositol (GPI) anchoring is important for the function of several proteins in the context of their membrane trafficking pathways. We have shown previously that endocytosed GPI-anchored proteins (GPI-APs) are recycled to the plasma membrane three times more slowly than other membrane components. Recently, we found that GPI-APs are delivered to endocytic organelles, devoid of markers of the clathrin-mediated pathway, prior to their delivery to a common recycling endosomal compartment (REC). Here we show that the rate-limiting step in the recycling of GPI-APs is their slow exit from the REC; replacement of the GPI anchor with a transmembrane protein sequence abolishes retention in this compartment. Depletion of endogenous sphingolipid levels using sphingolipid synthesis inhibitors or in a sphingolipid-synthesis mutant cell line specifically enhances the rate of endocytic recycling of GPI-APs to that of other membrane components. We have shown previously that endocytic retention of GPI-APs is also relieved by cholesterol depletion. These findings strongly suggest that functional retention of GPI-APs in the REC occurs via their association with sphingolipid and cholesterol-enriched sorting platforms or 'rafts'.

Original languageEnglish
Pages (from-to)1583-1592
Number of pages10
JournalEMBO Journal
Volume20
Issue number7
DOIs
StatePublished - Apr 2 2001
Externally publishedYes

Fingerprint

Glycosylphosphatidylinositols
Sphingolipids
Recycling
Endocytosis
Proteins
Membranes
Cholesterol
Clathrin
Cell membranes
Sorting
Organelles
Cells
Cell Membrane
Association reactions
Cell Line

Keywords

  • Endocytosis
  • GPI-anchored proteins
  • Rafts
  • Sorting
  • Sphingolipids

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

GPI anchoring leads to sphingolipid-dependent retention of endocytosed proteins in the recycling endosomal compartment. / Chatterjee, Samit; Smith, Elizabeth R.; Hanada, Kentaro; Stevens, Victoria L.; Mayor, Satyajit.

In: EMBO Journal, Vol. 20, No. 7, 02.04.2001, p. 1583-1592.

Research output: Contribution to journalArticle

Chatterjee, Samit ; Smith, Elizabeth R. ; Hanada, Kentaro ; Stevens, Victoria L. ; Mayor, Satyajit. / GPI anchoring leads to sphingolipid-dependent retention of endocytosed proteins in the recycling endosomal compartment. In: EMBO Journal. 2001 ; Vol. 20, No. 7. pp. 1583-1592.
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