Evidence for a clathrin-mediated recycling of albumin in human term placenta.
During human pregnancy, the trophoblast layer is in direct contact with maternal albumin. In contrast to immunoglobulins, albumin does not cross the placental barrier. However, albumin affects the trophoblast placental lactogen and chorionic gonadotroph secretion. The present study investigated the interaction between albumin and syncytiotrophoblast using human term placental explants. Bovine serum albumin, labeled with either 125I or fluorescein isothio-cyanate, was taken up rapidly by placental explants. This process was temperature-sensitive. The internalized labeled BSA quickly outflowed from the tissue at the maternal side, largely without any major modification in molecular weight. Colchicine (1 mM), which disrupts the microtubule network, or cytochalasin B (40 microM), which disassembles filamentous actin, did not interfere with the placental transmembrane movements of labeled BSA. Megalin, clathrin, and caveolin 1 are three membrane proteins associated with albumin endocytosis in other tissues, but only megalin and clathrin were detected in the syncytiotrophoblast layer by immunohistochemistry. The uptake of labeled BSA into placental explants was not modified by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (1 mM) or 5-nitro-2-(3-phenylpropylamino)benzoic acid (100 microM), two pharmacological tools known to disturb megalin-mediated albumin endocytosis. By contrast, methyl-beta-cyclodextrin (10 mM) and chlorpromazine (1.4 mM), both of which disrupt the clathrin-mediated endocytotic system, significantly reduced the uptake of labeled BSA. These data suggest, to our knowledge for the first time, that maternal albumin is actively internalized into the human trophoblast according to an apical recycling pathway. This temperature-sensitive process does not depend on an intact cytoskeleton, but it is associated with a clathrin-mediated endocytotic system.
Laboratory of Experimental Hormonology, Université Libre de Bruxelles, B-1070 Brussels, Belgium. nlambot@ulb.ac.be
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N
Lambot
P
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Lybaert
A
A
Boom
J
J
Delogne-Desnoeck
A M
AM
Vanbellinghen
G
G
Graff
P
P
Lebrun
S
S
Meuris
D051242:Caveolin 1 / Q000032:analysis; D002966:Clathrin / Q000032:analysis / Q000378:metabolism*; D004705:Endocytosis; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000032:analysis; D008431:Maternal-Fetal Exchange; D018613:Microscopy, Confocal; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism
D051242:Caveolin 1; D002966:Clathrin; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D012710:Serum Albumin, Bovine