Transgelin 2 is required for embryo implantation by promoting actin polymerization

Liang, Xiaoling; Jin, Yimei; Wang, Hao; Meng, Xinlu; Tan, Zhongzhou; Huang, Tao; Fan, Shang­rong

doi:10.1096/fj.201802158rrr

Cited by 31 publications

(35 citation statements)

References 45 publications

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“…Actin is crucial in determining cell proliferation and invasion, mainly by F‐actin polymerization and rearrangement of the actin cytoskeleton . Recent studies suggest that PAR‐1 activation is regulated by EPCR, which mediates the polymerization of F‐actin and cortical actin distribution .…”

Section: Resultsmentioning

confidence: 99%

“…Actin is crucial in determining cell proliferation and invasion, mainly by F-actin polymerization and rearrangement of the actin cytoskeleton. 27 Recent studies suggest that PAR-1 activation is regulated by EPCR, 28 which mediates the polymerization of F-actin and cortical actin distribution. 29 Therefore, we next investigated whether EPCR knockout affects actin polymerization by activating PAR-1-mediated cell signalling.…”

Section: Epcr Regulates Actin Polymerizationmentioning

confidence: 99%

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Down‐regulation of endothelial protein C receptor promotes preeclampsia by affecting actin polymerization

Wang

Liang

et al. 2020

J Cellular Molecular Medi

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Preeclampsia is a severe pregnancy‐related disease that is found in 3%–5% of pregnancies worldwide and is primarily related to the decreased proliferation and invasion of trophoblast cells and abnormal uterine spiral artery remodelling. However, studies on the pathogenesis of placental trophoblasts are insufficient, and the aetiology of PE remains unclear. Here, we report that endothelial protein C receptor (EPCR), a transmembrane glycoprotein, was down‐regulated in placentas from preeclamptic patients. Moreover, lack of EPCR significantly reduced the trophoblast cell proliferation, invasion and tube formation capabilities. Microscale thermophoresis analysis showed that EPCR directly bound to protease‐activated receptor 1 (PAR‐1), a G protein‐coupled receptor. This change resulted in a substantial reduction in active Rac1 and caused excessive actin rearrangement. Our findings reveal a previously unidentified role of EPCR in the regulation of trophoblast proliferation, invasion and tube formation through promotion of actin polymerization, which is required for normal placental development.

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Section: Resultsmentioning

confidence: 99%

Section: Epcr Regulates Actin Polymerizationmentioning

confidence: 99%

Down‐regulation of endothelial protein C receptor promotes preeclampsia by affecting actin polymerization

Wang

Liang

et al. 2020

J Cellular Molecular Medi

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“…As a member of the transgelin family, TAGLN2 plays a significant role in the regulation of F-actin remodeling, which is important for trophoblast cell adhesion and invasion. TAGLN2 may be a potential target to improve embryo implantation rates in in vitro fertilization (41). Furthermore, the significantly upregulated proteins FN1, FGL1, and THBS1 are also seemingly involved in the establishment and maintenance of pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Label-Free Mass Spectrometry-Based Quantitative Proteomics Analysis of Serum Proteins During Early Pregnancy in Jennies (Equus asinus)

Liang¹,

Han²,

Tang³

et al. 2020

Front. Vet. Sci.

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Early pregnancy in jennies is routinely determined by palpation per rectum or ultrasonography and also by detecting steroid hormone and chorionic gonadotropin levels in the blood, plasma, and serum. Herein we applied label-free mass spectrometry-based quantitative proteomics to identify serum proteins that were differentially expressed between early pregnant (day 45 after ovulation) and non-pregnant jennies. Bioinformatics analysis allowed illustration of pathways potentially involved in early pregnancy. We identified 295 proteins from a total of 2,569 peptides. Twenty-five proteins (22 upregulated and three downregulated) were significantly differentially expressed between the early pregnant and non-pregnant groups. The majority of the differentially expressed proteins were involved in defense response, early embryonic development, and hormone signaling pathways. Furthermore, functional protein analyses suggested that proteins were involved in binding, enzyme inhibitor activity, and enzyme regulator activity. Five serum proteins-granulin precursor/acrogranin, transgelin-2, fibronectin, fibrinogen-like 1, and thrombospondin 1-can be considered as novel, reliable candidates to detect pregnancy in jennies. To the best of our knowledge, this is the first study to use label-free mass spectrometry-based quantitative proteomics to analyze serum proteins during early pregnancy in jennies. Our results should facilitate the identification of valuable pregnancy diagnostic markers in early pregnant jennies.

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“…Transgelin-2 has been implicated in various processes including tumorigenesis, cell migration/invasion, proliferation, differentiation, and embryo implantation (Yoshino et al 2011;Yakabe et al 2016;Jeon et al 2018;Liang et al 2019;Liu et al 2019), but its mechanistic basis remains elusive. Transgelin-2 is known for its ability to polymerize G-actin and crosslink F-actin, which may eventually contribute -as many other ABPs that account for ~25% of the total cellular protein do (Pollard 2016;Lappalainen 2016;Jo et al 2018;Kim et al 2018 Specifically, among the known five types of CH domains, transgelin-2 has type-3 CH domain (Gimona et al 2002) that is actually unable to bind F-actin in vitro (Gimona and Mital 1998;Fu et al 2000;Goodman et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Determining the inherent reaction-diffusion properties of actin-binding proteins in cells by incorporating genetic engineering to FRAP-based framework

Saitô

Matsunaga

Matsui

et al. 2020

Preprint

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Proteins in cells undergo repeated association to other molecules, thereby reducing the apparent extent of their intracellular diffusion. While much effort has been made to analytically decouple these combined effects of pure diffusion and chemical reaction, it is difficult to attribute the measured quantities to the nature of specific domains of the probed proteins particularly if, as is often the case, the protein has multiple domains to independently interact with the same types but different molecules. Motivated by the common goal in cell signaling research aimed at identifying the protein domains responsible for particular intermolecular interactions, here we describe a new approach to determining the domain-level reaction and pure diffusion properties. To validate this methodology, we apply it to transgelin-2, an actin-binding protein whose intracellular dynamics remains elusive. We develop a fluorescence recovery after photobleaching (FRAP)-based framework, in which comprehensive combinations of domain-deletion mutants are created with genetic engineering, and the difference among the mutants in FRAP response is analyzed. We demonstrate that transgelin-2 in cells interacts with F-actin via two separate domains, and the chemical equilibrium constant of the interaction is determined at the individual domain levels. Its pure diffusion properties independent of the association to F-actin is also obtained. This approach requires some effort to construct the mutants, but instead enables in situ domain-level determination of the physicochemical properties, which will be useful, as specifically shown here for transgelin-2, in addressing the signaling mechanism of cellular proteins.

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Transgelin 2 is required for embryo implantation by promoting actin polymerization

Cited by 31 publications

References 45 publications

Down‐regulation of endothelial protein C receptor promotes preeclampsia by affecting actin polymerization

Down‐regulation of endothelial protein C receptor promotes preeclampsia by affecting actin polymerization

Label-Free Mass Spectrometry-Based Quantitative Proteomics Analysis of Serum Proteins During Early Pregnancy in Jennies (Equus asinus)

Determining the inherent reaction-diffusion properties of actin-binding proteins in cells by incorporating genetic engineering to FRAP-based framework

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