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ARHGEF18/p114RhoGEF coordinates PKA/CREB signalling and actomyosin remodelling to promote trophoblast cell-cell fusion during placenta morphogenesis
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Beal, Robert, Alonso-Carriazo, Fernandez, Grammatopoulos, Dimitris, Matter, Karl and Balda, Maria S. (2021) ARHGEF18/p114RhoGEF coordinates PKA/CREB signalling and actomyosin remodelling to promote trophoblast cell-cell fusion during placenta morphogenesis. Frontiers in Cell and Developmental Biology, 9 . 658006. doi:10.3389/fcell.2021.658006 ISSN 2296-634X.
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Official URL: http://dx.doi.org/10.3389/fcell.2021.658006
Abstract
Coordination of cell-cell adhesion, actomyosin dynamics and gene expression is crucial for morphogenetic processes underlying tissue and organ development. Rho GTPases are main regulators of the cytoskeleton and adhesion. They are activated by guanine nucleotide exchange factors in a spatially and temporally controlled manner. However, the roles of these Rho GTPase activators during complex developmental processes are still poorly understood. ARHGEF18/p114RhoGEF is a tight junction-associated RhoA activator that forms complexes with myosin II, and regulates actomyosin contractility. Here we show that p114RhoGEF/ARHGEF18 is required for mouse syncytiotrophoblast differentiation and placenta development. In vitro and in vivo experiments identify that p114RhoGEF controls expression of AKAP12, a protein regulating protein kinase A (PKA) signaling, and is required for PKA-induced actomyosin remodeling, cAMPresponsive element binding protein (CREB)-driven gene expression of proteins required for trophoblast differentiation, and, hence, trophoblast cell-cell fusion. Our data thus indicate that p114RhoGEF links actomyosin dynamics and cell-cell junctions to PKA/CREB signaling, gene expression and cell-cell fusion.
Item Type: | Journal Article | |||||||||
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Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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Library of Congress Subject Headings (LCSH): | Cell adhesion, Gene expression, Protein binding, G proteins, Rho GTPases | |||||||||
Journal or Publication Title: | Frontiers in Cell and Developmental Biology | |||||||||
Publisher: | Frontiers Media | |||||||||
ISSN: | 2296-634X | |||||||||
Official Date: | 25 March 2021 | |||||||||
Dates: |
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Volume: | 9 | |||||||||
Article Number: | 658006 | |||||||||
DOI: | 10.3389/fcell.2021.658006 | |||||||||
Status: | Peer Reviewed | |||||||||
Publication Status: | Published | |||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||
Date of first compliant deposit: | 9 March 2021 | |||||||||
Date of first compliant Open Access: | 13 April 2021 | |||||||||
RIOXX Funder/Project Grant: |
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