The glycophospholipid-linked folate receptor internalizes folate without entering the clathrin-coated pit endocytic pathway.
The folate receptor, also known as the membrane folate-binding protein, is maximally expressed on the surface of folate-depleted tissue culture cells and mediates the high affinity accumulation of 5-methyltetrahydrofolic acid in the cytoplasm of these cells. Recent evidence suggests that this receptor recycles during folate internalization and that it is anchored in the membrane by a glycosyl-phosphatidylinositol linkage. Using quantitative immunocytochemistry, we now show that (a) this receptor is highly clustered on the cell surface; (b) these clusters are preferentially associated with uncoated membrane invaginations rather than clathrin-coated pits; and (c) the receptor is not present in endosomes or lysosomes. This receptor appears to physically move in and out of the cell using a novel uncoated pit pathway that does not merge with the clathrin-coated pit endocytic machinery.
Rothberg
K G
KG
Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical Center, Dallas 75235.
Ying
Y S
YS
Kolhouse
J F
JF
Kamen
B A
BA
Anderson
R G
RG
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism* / Q000648:ultrastructure; D002460:Cell Line; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism* / Q000648:ultrastructure; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000378:metabolism*; D005613:Freeze Etching; D006017:Glycolipids / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols; D006801:Humans; D007624:KB Cells; D008854:Microscopy, Electron; D010716:Phosphatidylinositols / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D005492:Folic Acid