Annexin-A5 organized in 2D-network at the plasmalemma eases human trophoblast fusion.
Only a limited number of human cells can fuse to form a multinucleated syncytium. Cell fusion occurs as part of the differentiation of some cell types, including myotubes in muscle and osteoclasts in remodeling bone. In the differentiation of the human placenta, mononuclear cytotrophoblasts aggregate and fuse to form endocrinologically active, non-proliferative, multinucleated syncytia. These syncytia allow the exchange of nutrients and gases between the maternal and fetal circulation. Alteration of syncytial formation during pregnancy affects fetal growth and the outcome of the pregnancy. Here, we demonstrate the role of annexin A5 (AnxA5) in syncytial formation by cellular delivery of recombinant AnxA5 and RNA interference. By a variety of co-immunoprecipitation, immunolocalization and proximity experiments, we show that a pool of AnxA5 organizes at the inner-leaflet of the plasma membrane in the vicinity of a molecular complex that includes E-Cadherin, α-Catenin and β-Catenin, three proteins previously shown to form adherens junctions implicated in cell fusion. A combination of knockdown and reconstitution experiments with AnxA5, with or without the ability to self-assemble in 2D-arrays, demonstrate that this AnxA5 2D-network mediates E-Cadherin mobility in the plasmalemma that triggers human trophoblasts aggregation and thereby cell fusion.
INSERM, U767, Cell fusion, Paris, F-75006 France.|Université Paris Descartes, Paris, F-75006 France.|PremUp, Paris, F-75006 France.
Severine A
SA
Degrelle
INSERM, U767, Cell fusion, Paris, F-75006 France.|Université Paris Descartes, Paris, F-75006 France.|UMR-S1180, Inserm, Univ. Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
Pascale
P
Gerbaud
UMR144, Institut Curie/CNRS, Cell and Tissue Imaging Platform, Paris, France.
Ludovic
L
Leconte
INSERM, U767, Cell fusion, Paris, F-75006 France.|Université Paris Descartes, Paris, F-75006 France.
Fatima
F
Ferreira
INSERM, U767, Cell fusion, Paris, F-75006 France.|Université Paris Descartes, Paris, F-75006 France.|PremUp, Paris, F-75006 France.|UMR-S1180, Inserm, Univ. Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
Guillaume
G
Pidoux
D022005:Adherens Junctions / Q000378:metabolism / Q000648:ultrastructure; D000328:Adult; D017304:Annexin A5 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D002459:Cell Fusion; D002462:Cell Membrane / Q000378:metabolism*; D002465:Cell Movement; D005260:Female; D005786:Gene Expression Regulation; D015726:Giant Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*; D051178:alpha Catenin / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
D017304:Annexin A5; D015703:Antigens, CD; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D034741:RNA, Small Interfering; D051178:alpha Catenin; D051176:beta Catenin