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 language | English |
|---|---|
| Pages (from-to) | 1583-1592 |
| Number of pages | 10 |
| Journal | EMBO Journal |
| Volume | 20 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 2 2001 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - GPI anchoring leads to sphingolipid-dependent retention of endocytosed proteins in the recycling endosomal compartment
AU - Chatterjee, Samit
AU - Smith, Elizabeth R.
AU - Hanada, Kentaro
AU - Stevens, Victoria L.
AU - Mayor, Satyajit
PY - 2001/4/2
Y1 - 2001/4/2
N2 - 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'.
AB - 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'.
KW - Endocytosis
KW - GPI-anchored proteins
KW - Rafts
KW - Sorting
KW - Sphingolipids
UR - http://www.scopus.com/inward/record.url?scp=0035794533&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035794533&partnerID=8YFLogxK
U2 - 10.1093/emboj/20.7.1583
DO - 10.1093/emboj/20.7.1583
M3 - Article
VL - 20
SP - 1583
EP - 1592
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 7
ER -