Silencing of dedicator of cytokinesis (<scp>DOCK</scp>180) obliterates pregnancy by interfering with decidualization due to blockage of nuclear entry of autoimmune regulator (<scp>AIRE</scp>)

Mohan, Jasna Jagan; Narayan, Prashanth; Padmanabhan, Renjini Ambika; Joseph, Selin; Kumar, Pratap; Laloraya, Malini

doi:10.1111/aji.12844

Cited by 5 publications

(6 citation statements)

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“…Both in its usual cytosolic location and in its nuclear location, DOCK1 has the ability to interact with ELMO proteins and activate Rac1 [18]. Moreover, a new nuclear function of DOCK1 has recently been discovered in the uterus, consisting of the nuclear import of the autoimmune regulator (AIRE), a mechanism that plays a role in decidualization [24].…”

Section: Discussionmentioning

confidence: 99%

Variable Distribution of DOCK-D Proteins between Cytosol and Nucleoplasm in Cell Lines, Effect of Interleukin-4 on DOCK10 in B-Cell Lymphoid Neoplasms, and Validation of a New DOCK10 Antiserum for Immunofluorescence Studies

et al. 2021

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Dedicator-of-cytokinesis (DOCK), a family of guanine-nucleotide exchange factors (GEFs), comprises four subfamilies, named from A to D. DOCK-D comprises DOCK9, DOCK10, and DOCK11. The GEF activity involves translocation from the cytoplasm to the plasma membrane (PM), as assessed by the transfection of tagged proteins. However, the cellular localization of endogenous DOCK proteins is poorly understood. In this paper, to gain a better understanding of the role of the DOCK-D proteins, we studied their distribution between cytosol and nucleoplasm in 11 cell lines. DOCK-D proteins were distributed with variable cytosolic or nuclear predominance, although the latter was common for DOCK9 and DOCK11. These results suggest that the DOCK-D proteins may perform new nuclear functions, which remain to be discovered. Furthermore, we found that DOCK10 levels are increased by interleukin-4 (IL-4) in B-cell lymphoid neoplasms other than chronic lymphocytic leukemia (CLL) such as mantle cell lymphoma and diffuse large B-cell lymphoma. We also found evidence for an induction of the cytosolic levels of DOCK10 by IL-4 in CLL. Finally, we obtained a valid DOCK10 antiserum for immunofluorescence (IF) microscopy that, as an antibody against the hemagglutinin (HA) tag, marked PM ruffles and filopodia in HeLa cells with inducible expression of HA-DOCK10.

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Section: Discussionmentioning

confidence: 99%

Variable Distribution of DOCK-D Proteins between Cytosol and Nucleoplasm in Cell Lines, Effect of Interleukin-4 on DOCK10 in B-Cell Lymphoid Neoplasms, and Validation of a New DOCK10 Antiserum for Immunofluorescence Studies

et al. 2021

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“…One morphometric analysis identified smaller implantation sites, compromised primary decidual zones, and reduced embryo sizes in AIRE-deficient female mice compared to WT control mice. Decidual markers; bone morphogenetic protein-2,4 (Bmp2, Bmp4) (30), which are focal to decidual reprogramming during early pregnancy; insulin-like growth factor-binding protein 1 (Igfbp1); and homeobox A10 (Hoxa10) (31) are conserved genes that regulate progesterone-induced regional decidualization in implantation and play key roles in the uterus and during pregnancy. AIRE is well-known to influence the transcription of these genes in the endometrial stromal cells by binding to their promoters.…”

Section: The Molecular Mechanisms Of Aire Deficiency In Female Infert...mentioning

confidence: 99%

The Role of AIRE Deficiency in Infertility and Its Potential Pathogenesis

et al. 2021

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The increasing number of patients with infertility is recognized as an emerging problem worldwide. However, little is known about the cause of infertility. At present, it is believed that infertility may be related to genetic or abnormal immune responses. It has long been indicated that autoimmune regulator (AIRE), a transcription factor, participates in immune tolerance by regulating the expression of thousands of promiscuous tissue-specific antigens in medullary thymic epithelial cells (mTECs), which play a pivotal role in preventing autoimmune diseases. AIRE is also expressed in germ cell progenitors. Importantly, the deletion of AIRE leads to severe oophoritis and age-dependent depletion of follicular reserves and causes altered embryonic development in female mice. AIRE-deficient male mice exhibit altered apoptosis during spermatogenesis and have a significantly decreased breeding capacity. These reports suggest that AIRE deficiency may be responsible for infertility. The causes may be related to the production of autoantibodies against sperm, poor development of germ cells, and abnormal ovarian function, which eventually lead to infertility. Here, we focus on the potential associations of AIRE deficiency with infertility as well as the possible pathogenesis, providing insight into the significance of AIRE in the development of infertility.

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“…Reports also showed the role of were studied (Kedia-Mokashi et al, 2011;Bhusane et al, 2016). Interesting insights were also provided into the post-implantation development of embryos and the molecular regulation of implantation and decidualization (Nimbkar-Joshi, et al, 2015;Padmanabhan and Laloraya, 2016;Mohan et al, 2018). Recently, one of the developmental pattern formation-associated genes viz., HOXA10 was shown to be involved in trophoblast invasion and embryo implantation (Ashary et al, 2018;Godbole et al, 2017).…”

Section: Embryo Development and Functionmentioning

confidence: 99%

Research on early mammalian development in India

Seshagiri¹,

Vani²

2020

Int. J. Dev. Biol.

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Historically, research in India on early mammalian development had only begun, rather modestly, in the last century, unlike the USA and UK. In India, initial studies were on gonadal and reproductive tissue development and function and they were limited to anatomical and histological characterization. This was followed by research on fertility regulation and contraception. Since the 1960s, a major initiative took place regarding endocrine biochemistry and the use of antifertility agents in inhibiting gonadal function and early development. Post-independence, the Indian government´s funding support enabled universities and institutions to embark on various research disciplines in biology but with no particular emphasis on developmental biology per se. Subsequently, India made significant progress in the area of mammalian reproduction and development, but not specifically in the core aspects of developmental biology. Reasons for this could be due to the nation’s compulsion to invest and embark on socio-economic and infrastructure development and on research involving family planning methods for reversible-affordable contraceptives to curtail population growth. With regard to the latter, biologists were involved in hormone-based contraception research. During this pursuit, insights were achieved into basic aspects of the development of gonads, gametes and embryos. Notwithstanding this, in the post-1980s through to the present time, Indian scientists have contributed to (i) the understanding of the cellular and molecular regulation of early development, (ii) developing genetically modified mouse models, (iii) using assisted reproductive technologies, generating mammalian progeny, including humans and (iv) deriving pluripotent stem cell lines for developmental studies. This article provides a perspective on the past and current status of early mammalian development research in India.

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Silencing of dedicator of cytokinesis (DOCK180) obliterates pregnancy by interfering with decidualization due to blockage of nuclear entry of autoimmune regulator (AIRE)

Abstract: DOCK180 has an indispensable role in pregnancy establishment as knocking down Dock180 abrogates pregnancy by a consolidated impact on decidualization and angiogenesis by regulating AIRE nuclear entry.

Cited by 5 publications

References 43 publications

Variable Distribution of DOCK-D Proteins between Cytosol and Nucleoplasm in Cell Lines, Effect of Interleukin-4 on DOCK10 in B-Cell Lymphoid Neoplasms, and Validation of a New DOCK10 Antiserum for Immunofluorescence Studies

Variable Distribution of DOCK-D Proteins between Cytosol and Nucleoplasm in Cell Lines, Effect of Interleukin-4 on DOCK10 in B-Cell Lymphoid Neoplasms, and Validation of a New DOCK10 Antiserum for Immunofluorescence Studies

The Role of AIRE Deficiency in Infertility and Its Potential Pathogenesis

Research on early mammalian development in India

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