IGF binding protein-1 (IGFBP-1) is preferentially associated with the fetal-facing basal surface of the syncytiotrophoblast in the human placenta.
IGF receptors are expressed in a spatially polarized manner on the syncytiotrophoblast cell membrane. We therefore examined the hypothesis that IGFBPs expressed at the maternal-fetal interface interact with distinct surfaces of the syncytiotrophoblast membrane to modulate IGF function. Membrane vesicles were prepared specifically from the maternal-facing, microvillous membrane (MVM) and the fetal-facing, basal membrane (BM) surfaces of the syncytiotrophoblast. The association of IGFBPs with each membrane preparation was determined by ligand blot analysis. A doublet migrating at 38/42 kD was detected in both MVM and BM preparations. Selective immunoprecipitation followed by ligand blot analysis identified this IGF binding species as IGFBP-3. Additionally, a protein migrating at approximately 29 kD was associated primarily with the BM. This protein was identified as IGFBP-1 by both immunoprecipitation and ligandblotting techniques. Non-denaturing PAGE revealed five distinct bands corresponding to different degrees of phosphorylation. The phosphorylation pattern of BM-associated IGFBP-1 was identical to that of native IGFBP-1 in amniotic fluid. Immunohistological analysis of term placenta revealed IGFBP-1-specific staining of the syncytiotrophoblast and the fetal capillary/pericapillary bed. The localization of IGFBP-1 to a distinct compartment within the fetal placenta, not in proximity to the syncytiotrophoblast type I IGF receptor, suggests it may play a role in regulating/targeting IGF activity within the stromal compartment or by exerting IGF-independent effects on the basal surface of the syncytiotrophoblast. The nature of its binding to the BM has not been determined.
Fang
J
J
Department of Pediatrics, University of Texas-Houston Health Science Center, Houston, Texas 77030, USA.
Furesz
T C
TC
Smith
C H
CH
Fant
M E
ME
D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D016023:Integrins / Q000032:analysis; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation; D010920:Placenta / Q000378:metabolism*; D011233:Precipitin Tests; D013002:Somatomedins / Q000378:metabolism
D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D016023:Integrins; D008565:Membrane Proteins; D013002:Somatomedins