Activated α2-macroglobulin binding to cell surface GRP78 induces trophoblastic cell fusion

Article Article scientifique Article Activated α2-macroglobulin binding to cell surface GRP78 induces trophoblastic cell fusion eng 2020 author Bastida Ruiz Daniel 759554 author Wuillemin-Rambosson Christine Gabrielle 119160 author Pederencino Aude 846918 author Yaron Michal 668428 author Martinez De Tejada Weber Begona 590919 author Pizzo Salvatore Vincent author Cohen Marie-Benoîte 0000-0003-4621-5464 135615 9666 10.1038/s41598-020-66554-0 32541810 2045-2322 http://www.nature.com/articles/s41598-020-66554-0 The villous cytotrophoblastic cells have the ability to fuse and differentiate, forming the syncytiotrophoblast (STB). The syncytialisation process is essential for placentation. Nevertheless, the mechanisms involved in cell fusion and differentiation are yet to be fully elucidated. It has been suggested that cell surface glucose-regulated protein 78 (GRP78) was involved in this process. In multiple cancer cells, cell membrane-located GRP78 has been reported to act as a receptor binding to the active form of α2-macroglobulin (α2M*), activating thus several cellular signalling pathways implicated in cell growth and survival. We hypothesised that GRP78 interaction with α2M* may also activate signalling pathways in trophoblastic cells, which, in turn, may promote cell fusion. Here, we observed that α2M mRNA is highly expressed in trophoblastic cells, whereas it is not expressed in the choriocarcinoma cell line BeWo. We thus took advantage of forskolin-induced syncytialisation of BeWo cells to study the effect of exogenous α2M* on syncytialisation. We first demonstrated that α2M* induced trophoblastic cell fusion. This effect is dependent on α2M*-GRP78 interaction, ERK1/2 and CREB phosphorylation, and unfolded protein response (UPR) activation. Overall, these data provide novel insights into the signalling molecules and mechanisms regulating trophoblastic cell fusion. Cell biology Developmental biology Dewey 618 58 Département de pédiatrie, gynécologie et obstétrique 223 false 584 Laboratoire de biologie des tumeurs gynécologiques et du développement 927 213 Martinez De Tejada Begona 272 150 L'imagerie cérébrale 184 Scientific Reports 10 1 a25d8248-ef09-4e73-8e03-8fb0c63e49f4 Article (Published version) Public Scientificreports.pdf 2645949 application/pdf CC BY bbe234c8-2635-4bb8-a545-771d218885ed Erratum Public s41598-025-13987-0.pdf 941241 application/pdf b872432a39e0c851c80d627217427aa5675b265890ea6d696e4231d4028f17f0 There was an error in the figure assembly of Figure 3A and 3C. 10.1038/s41598-025-13987-0 40770026 openAccess Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

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Activated α2-macroglobulin binding to cell surface GRP78 induces trophoblastic cell fusion	Scientific Reports			2020	418	183

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