GPI-anchored proteins are delivered to recycling endosomes via a distinct cdc42-regulated, clathrin-independent pinocytic pathway.
Endocytosis of cell-surface proteins via specific pathways is critical for their function. We show that multiple glycosylphosphatidylinositol-anchored proteins (GPI-APs) are endocytosed to the recycling endosomal compartment but not to the Golgi via a nonclathrin, noncaveolae mediated pathway. GPI anchoring is a positive signal for internalization into rab5-independent tubular-vesicular endosomes also responsible for a major fraction of fluid-phase uptake; molecules merely lacking cytoplasmic extensions are not included. Unlike the internalization of detergent-resistant membrane (DRM)-associated interleukin 2 receptor, endocytosis of DRM-associated GPI-APs is unaffected by inhibition of RhoA or dynamin 2 activity. Inhibition of Rho family GTPase cdc42, but not Rac1, reduces fluid-phase uptake and redistributes GPI-APs to the clathrin-mediated pathway. These results describe a distinct constitutive pinocytic pathway, specifically regulated by cdc42.
Sabharanjak
Shefali
S
National Centre for Biological Sciences, UAS-GKVK Campus, Bellary Road, 560 065, Bangalore, India.
Sharma
Pranav
P
Parton
Robert G
RG
Mayor
Satyajit
S
D000818:Animals; D015415:Biomarkers; D019556:COS Cells; D021941:Caveolae / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D003902:Detergents; D011992:Endosomes / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D010873:Pinocytosis / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
D015415:Biomarkers; D002966:Clathrin; D003902:Detergents; D017261:Glycosylphosphatidylinositols; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D015375:Receptors, Interleukin-2; D049452:Green Fluorescent Proteins; D020764:cdc42 GTP-Binding Protein; D020696:rab5 GTP-Binding Proteins