title: Spatiotemporal regulation of cAMP signaling controls the human trophoblast fusion.
abstract: During human placentation, mononuclear cytotrophoblasts fuse to form multinucleated syncytia ensuring hormonal production and nutrient exchanges between the maternal and fetal circulation. Syncytial formation is essential for the maintenance of pregnancy and for fetal growth. The cAMP signaling pathway is the major route to trigger trophoblast fusion and its activation results in phosphorylation of specific intracellular target proteins, in transcription of fusogenic genes and assembly of macromolecular protein complexes constituting the fusogenic machinery at the plasma membrane. Specificity in cAMP signaling is ensured by generation of localized pools of cAMP controlled by cAMP phosphodiesterases (PDEs) and by discrete spatial and temporal activation of protein kinase A (PKA) in supramolecular signaling clusters inside the cell organized by A-kinase-anchoring proteins (AKAPs) and by organization of signal termination by protein phosphatases (PPs). Here we present original observations on the available components of the cAMP signaling pathway in the human placenta including PKA, PDE, and PP isoforms as well as AKAPs. We continue to discuss the current knowledge of the spatiotemporal regulation of cAMP signaling triggering trophoblast fusion.
authors.affiliation: INSERM, UMR-S-1139, Group Cell Fusion, Université Paris Descartes Paris, France ; Université Paris Descartes Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Gerbaud
authors.affiliation: Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital Oslo, Norway ; Biotechnology Centre, University of Oslo Oslo, Norway ; K.G. Jebsen Inflammation Research Centre, University of Oslo Oslo, Norway ; K.G. Jebsen Centre for Cancer Immunotherapy, University of Oslo Oslo, Norway ; Department of Infectious Diseases, Oslo University Hospital Oslo, Norway.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Taskén
authors.affiliation: INSERM, UMR-S-1139, Group Cell Fusion, Université Paris Descartes Paris, France ; Université Paris Descartes Paris, France ; INSERM, U1180 Châtenay-Malabry, France ; Faculté de Pharmacie, Université Paris-Sud Châtenay-Malabry, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pidoux
keywords: AKAPs; cAMP; phosphatases; phosphodiesterases; placenta; protein kinase A; trophoblast fusion