Differential sorting and fate of endocytosed GPI-anchored proteins.
In this paper, we studied the fate of endocytosed glycosylphosphatidyl inositol anchored proteins (GPI- APs) in mammalian cells, using aerolysin, a bacterial toxin that binds to the GPI anchor, as a probe. We find that GPI-APs are transported down the endocytic pathway to reducing late endosomes in BHK cells, using biochemical, morphological and functional approaches. We also find that this transport correlates with the association to raft-like membranes and thus that lipid rafts are present in late endosomes (in addition to the Golgi and the plasma membrane). In marked contrast, endocytosed GPI-APs reach the recycling endosome in CHO cells and this transport correlates with a decreased raft association. GPI-APs are, however, diverted from the recycling endosome and routed to late endosomes in CHO cells, when their raft association is increased by clustering seven or less GPI-APs with an aerolysin mutant. We conclude that the different endocytic routes followed by GPI-APs in different cell types depend on the residence time of GPI-APs in lipid rafts, and hence that raft partitioning regulates GPI-APs sorting in the endocytic pathway.
Fivaz
Marc
M
Department of Genetics and Microbiology, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland.
Vilbois
Francis
F
Thurnheer
Sarah
S
Pasquali
Christian
C
Abrami
Laurence
L
Bickel
Perry E
PE
Parton
Robert G
RG
van der Goot
F Gisou
FG
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D016466:CHO Cells / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003902:Detergents / Q000494:pharmacology; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D007668:Kidney; D021962:Membrane Microdomains / Q000502:physiology*; D008647:Mesocricetus; D052899:Pore Forming Cytotoxic Proteins; D021381:Protein Transport / Q000502:physiology*; D012995:Solubility
D001427:Bacterial Toxins; D003902:Detergents; D017261:Glycosylphosphatidylinositols; D052899:Pore Forming Cytotoxic Proteins; C032676:aerolysin