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The in vivo fusion process in the placenta is reproducible in vitro using purified human CTs, which aggregate and then fuse to form non-proliferative, multinucleated, endocrine active syncytiotrophoblasts (STs; Figure 1; Kliman et al., 1986).
Numerous proteins have been reported to be implicated in cell fusion processes such as tight junction, adherens junction, and gap junction proteins (Coutifaris et al., 1991; Dahl et al., 1995; Mbalaviele et al., 1995; Ilvesaro et al., 2000; Frendo et al., 2003; Charrasse et al., 2007; Pidoux et al., 2010). Model of cultured villous trophobasts purified from human placenta. VCT for villous cytotrophoblast, ST for syncytiotrophoblast, and EVT for extravillous trophoblast. Cytotrophoblasts (CT) aggregate after 24 to 48 h of culture, and fuse into a ST after 72 h, which secretes human chorionic gonadotropin (h CG) and human placental lactogen (h PL).
Although occurring in a variety of biological contexts, different fusion processes share many of the same steps that are tightly regulated in space and time (Pérot et al., 2011). Spatiotemporal dynam of h CG/c AMP signaling and regulation of placental function. doi: 10.1016/j.placenta.20 Pub Med Abstract | Cross Ref Full Text | Google Scholar Xiong, L.
Human embryo implantation requires placentation, a process in which fetal cytotrophoblasts (CT) invade the maternal endometrium to form an interphase with the maternal circulation, ensuring effective exchange of gases, nutrients, and the secretion of pregnancy-specific hormones (i.e., h CG: human chorionic gonadotropin and h PL: human placental lactogen) (Eaton and Contractor, 1993; Ogren and Talamentes, 1994; Benirschke and Kaufmann, 2000). doi: 10.1083/jcb.147.7.1481 Pub Med Abstract | Cross Ref Full Text | Google Scholar Weedon-Fekjær, M.
Immunocytofluorescence was performed as described previously (Pidoux et al., 2014). Cell signaling in space and time: where proteins come together and when they’re apart. doi: 10.1126/science.1175668 Pub Med Abstract | Cross Ref Full Text | Google Scholar Shi, Q., Lei, Z., Rao, C., and Lin, J. Novel role of human chorionic gonadotropin in differentiation of human cytotrophoblasts. doi: 10.1210/endo.132.3.7679981 Pub Med Abstract | Cross Ref Full Text | Google Scholar Tasken, K., and Aandahl, E.
Cell fusion was quantified by trophoblast fusion assays as described previously (Pidoux et al., 2014). doi: 10.1016/S0960-9822(99)80141-9 Pub Med Abstract | Cross Ref Full Text | Google Scholar Scott, J.
Both AC and PDE establish in c AMP microdomains within the cell (Zaccolo and Pozzan, 2002).
Furthermore, A-kinase anchoring proteins (AKAPs) provide through PKA anchoring a spatial regulation of the c AMP/PKA signaling by placing the kinase in the vicinity substrates. Reciprocal regulation of m RNA and protein for subunits of c AMP-dependent protein kinase (RI alpha and C alpha) by c AMP in a neoplastic B cell line (Reh).
Little is known about AKAP proteins underlying the spatio-temporal regulation of the c AMP-induced human cytrophoblast fusion and regulation of endocrine functions in the placenta.
Here we present original observations on the available components of the c AMP signaling pathway in the human placenta including PKA, PDE, and PP isoforms as well as AKAPs. doi: 10.1093/humrep/deq190 Pub Med Abstract | Cross Ref Full Text | Google Scholar Zaccolo, M., and Pozzan, T. Discrete microdomains with high concentration of c AMP in stimulated rat neonatal cardiac myocytes. doi: 10.1126/science.1069982 Pub Med Abstract | Cross Ref Full Text | Google Scholar Zambonin Zallone, A., Teti, A., and Primavera, M. Monocytes from circulating blood fuse in vitro with purified osteoclasts in primary culture. The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.
We continue to discuss the current knowledge of the spatiotemporal regulation of c AMP signaling triggering trophoblast fusion. No use, distribution or reproduction is permitted which does not comply with these terms.