Placental 57-kDa Ca(2+)-binding protein: regulation of expression and function in trophoblast calcium transport.
During gestation, transport by placental trophoblasts is solely responsible for nutrient supply to the developing fetus. The calcium (Ca) transport machinery of the placenta thus represents the primary tissue site for regulating fetal Ca homeostasis. The exact mechanism of trophoblast Ca transport is not known. However, there is evidence suggesting that a developmentally expressed cytosolic, trophoblast-specific, high M(r) 57-kDa Ca-binding protein (CaBP) plays an important role in regulating and/or shuttling cytosolic Ca. We report here the cloning of a full-length cDNA of the mouse CaBP which shows significant homology with calreticulin, an endoplasmic reticulum-associated Ca binding protein. The functional role of CaBP in cellular Ca handling was investigated using a trophoblastic cell line, Rcho-1, derived from a rat choriocarcinoma. Upon differentiation, Rcho-1 cells exhibit enhanced Ca uptake compared to undifferentiated Rcho-1 stem cells, and CaBP expression is upregulated. To analyze the regulation of CaBP expression, placenta organ cultures and Rcho-1 cells were treated for 48 h in vitro with a series of agents implicated in Ca homeostasis. In both placenta organ cultures and undifferentiated as well as differentiated Rcho-1 cells, treatment with 1,25-dihydroxy vitamin D3, estrogen, parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP 1-34), and Ca had no effect on CaBP mRNA and protein levels, which were significantly stimulated by PTHrP 67-84. PTHrP 67-84-treated Rcho-1 cells also exhibited higher Ca uptake activity than untreated control cells. The upregulation of CaBP expression during and/or following the differentiation of Rcho-1 cells into trophoblastic giant cells supports the importance of CaBP in trophoblast maturation and the validity of the Rcho-1 rat model cell system. In addition, the action of PTHrP on placental trophoblast Ca transport is likely to involve the regulation of CaBP expression to handle the increasing Ca requirements of the developing fetus.
Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
M E
ME
Hershberger
R S
RS
Tuan
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D037282:Calreticulin; D002454:Cell Differentiation; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006706:Homeostasis; D051379:Mice; D008969:Molecular Sequence Data; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D012261:Ribonucleoproteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014327:Trophoblasts / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D037282:Calreticulin; D018076:DNA, Complementary; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D012261:Ribonucleoproteins; C113608:calcium-binding protein, 57-kDa; C113609:parathyroid hormone-related protein (67-84); D002118:Calcium