title: GPI anchoring leads to sphingolipid-dependent retention of endocytosed proteins in the recycling endosomal compartment.
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'.
authors: National Center for Biological Sciences, UAS-GKVK Campus, Bellary Road, Bangalore 560 065, India.
authors: S
authors: S
authors: Chatterjee
authors: E R
authors: ER
authors: Smith
authors: K
authors: K
authors: Hanada
authors: V L
authors: VL
authors: Stevens
authors: S
authors: S
authors: Mayor
mesh_terms: D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism; D006224:Cricetinae; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D058973:Folate Receptors, GPI-Anchored; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin / Q000378:metabolism; D013107:Sphingolipids / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D017261:Glycosylphosphatidylinositols; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D013107:Sphingolipids