Direct Evidence for the Action of Phosphatidylinositol (3,4,5)-Trisphosphate-Mediated Signal Transduction in the 2-Cell Mouse Embryo1

Li, Yan; Chandrakanthan, Vashe; Day, Margot L.; O’Neill, Chris

doi:10.1095/biolreprod.107.060129

Cited by 32 publications

(56 citation statements)

References 74 publications

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“…Direct infusion of PIP3 (1,2-dipalmitoyl-sn-glyceryl-3-phosphatidylinositol-3,4,5-trisphosphate) into the cytoplasm of the two-cell embryo mimicked the action of Paf in inducing the activity of this current and membrane hyperpolarization. Furthermore, infusion of a PIP3 blocking antibody (monoclonal RC6F8) into the two-cell embryo blocked the expression of this hyperpolarizing current and also blocked the Paf-induced calcium transients (heat-treated antibody had no effect on these responses to Paf) (Li et al 2007b). These results show that Paf acted to induce the phospholipid kinase activity of PI3 kinase in the twocell embryo.…”

Section: Activation Of Pi3 Kinase By Ligand Receptorsmentioning

confidence: 71%

“…The calcium transient induced by Paf was accompanied by a marked hyperpolarization of membrane potential and this was caused by a net outward ion current (w280 pA). This current is composed of a 4,4 0 -diisothiocyanatostilbene-2,2 0 -disulfonate-sensitive (anion channel blocker) and tetraethylammonium chloride-sensitive (KC channel blocker) channels (Li et al 2007b(Li et al , 2007c. Direct infusion of PIP3 (1,2-dipalmitoyl-sn-glyceryl-3-phosphatidylinositol-3,4,5-trisphosphate) into the cytoplasm of the two-cell embryo mimicked the action of Paf in inducing the activity of this current and membrane hyperpolarization.…”

Section: Activation Of Pi3 Kinase By Ligand Receptorsmentioning

confidence: 99%

“…Phospholipase C-g (PLC-g) is a PH domain protein and may be important in the context of Paf-mediated calcium signaling. The two PLC-g genes (Plcg1 and 2; Li et al 2007b) and immunodetectable PLC-g are expressed in the early embryo (Li et al 2007b, Wang et al 2007 (Emerson et al 2000). Selective inhibition of PLC inhibits Paf-induced calcium transients (Emerson et al 2000).…”

Section: Downstream Effectors Of Pip3 Signalingmentioning

confidence: 99%

“…The two-cell mouse embryo expresses the three genes that code for AKT (Akt1-3) (Li et al 2007b) and immunostaining showed that AKT protein is expressed throughout the preimplantation stage (Riley et al 2005, Li et al 2007b. PIP3 can activate PDK, which in turn phosphorylates PIP3-bound AKT.…”

Section: Downstream Effectors Of Pip3 Signalingmentioning

confidence: 99%

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Phosphatidylinositol 3-kinase signaling in mammalian preimplantation embryo development

O’Neill

2008

Reproduction

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The development of the preimplantation mammalian embryo is an autopoietic process; once initiated development proceeds without an absolute requirement for external information or growth cues. This developmental autonomy is partly explained by the generation of autocrine trophic ligands that are released and act back on the embryo via specific receptors. Several embryotrophic ligands cause receptor-dependent activation of 1-o-phosphatidylinositol 3-kinase. This enzyme phosphorylates phosphatidylinositol-4,5-bisphosphate to form phosphatidylinositol-3,4,5-trisphosphate. Genetic or pharmacological ablation of this enzyme activity disrupts normal development of preimplantation embryos. Phosphatidylinositol-3,4,5-trisphosphate is a membrane lipid that acts as a docking site for a wide range of proteins possessing the pleckstrin homology (PH) domain. Such proteins are important regulators of cell survival, proliferation, and differentiation. RAC-a serine/threonine protein kinase is an important PH domain protein and its activity is required for normal preimplantation embryo development and survival. The activity of a range of PH domain proteins is also implicated in the normal development of the embryo. This review critically examines the evidence for the activation of 1-o-phosphatidylinositol 3-kinase in the generation of pleiotypic trophic response to embryotrophins in the autopoietic development of the preimplantation embryo.

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Section: Activation Of Pi3 Kinase By Ligand Receptorsmentioning

confidence: 71%

Section: Activation Of Pi3 Kinase By Ligand Receptorsmentioning

confidence: 99%

Section: Downstream Effectors Of Pip3 Signalingmentioning

confidence: 99%

Section: Downstream Effectors Of Pip3 Signalingmentioning

confidence: 99%

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Phosphatidylinositol 3-kinase signaling in mammalian preimplantation embryo development

O’Neill

2008

Reproduction

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“…plays critical roles at various stages of preimplantation development, including fertilization (McGuinness et al 1996, Day et al 2000, and during signaling by embryotrophic factors during later stages (Li et al 2007, O'Neill 2008. There is also evidence implicating monovalent cations (Na C and K C ) in the temporal (Day et al 1993(Day et al , 1998 and spatial (Wiley 1984, Wiley et al 1990 programing of early development.…”

Section: Cmentioning

confidence: 99%

Changing expression of chloride channels during preimplantation mouse development

et al. 2013

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Plasma membrane chloride channels (ClCs) play important roles in a broad range of cellular processes including cell volume regulation, proliferation, and transepithelial transport, all of which are critical during preimplantation embryonic development. In this study, the molecular and functional expression of voltage-gated ClCs was analyzed throughout preimplantation development of the mouse conceptus. mRNA transcripts for all Clcn genes were detected. Only Clcn1 mRNA showed differential expression in the blastocyst, being detected in the trophectoderm but not in the inner cell mass. CLCN3 protein was detected at low levels in the cytoplasm and plasma membrane in 4-cell embryos and was localized to the apical plasma membrane of the trophoblasts in the blastocyst. Whole-cell patchclamp recordings demonstrated the presence of a DIDS-sensitive, outwardly rectifying Cl K current throughout development, with this conductance being large at the 1-cell, morula and blastocyst stages. A second DIDS-insensitive Cl K current, which was inactivated by membrane depolarization, was present in cells differentiating into the trophoblast lineage and during blastocyst expansion. Inhibition of the DIDS-sensitive current and the DIDS-insensitive current, with 9-AC, prevented blastocyst expansion.

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Optogenetic Control of Phosphatidylinositol (3,4,5)‐Triphosphate Production by Light‐Sensitive Cryptochrome Proteins on the Plasma Membrane

et al. 2021

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Protein-protein interactions | Protein engineering | Fluorescent probes | Optogenetic control | Phosphatidylinosito| (3,4,5)-triphosphate Phosphatidylinositol (3,4,5)-triphosphate ( PIP3), acting as a fundamental second messenger, is emerging as a promising biomarker for disease diagnosis and prognosis. However, the real time analysis of phosphoinositide in living cells remains a key challenge owing to the low basal abundance and its fast metabolic rate. Herein, we design an optogenetic system that uses light sensitive protein-protein interaction between Arabidopsis cryptochrome 2 (CRY2) and CIB1 to spatiotemporally visualize the PIP3 production with sub-second timescale. In this system, a CIBN is anchored on the plasma membrane, whereas a CRY2 fused with a constitutively active PI3-kinase (acPI3K) would be driven from the cytosol to the membrane by the blue-light-activated CRY2-CIB1 interaction upon light irradiation. The PIP3 production is visualized via a fused fluorescent protein by the translocation of a Pleckstrin Homology (PH) domain (GRP1) from the cytosol to the plasma membrane with high specificity. We demonstrated the fast dynamics and reversibility of the optogenetic system initiated PIP3 synthesis on the plasma membrane. Notably, the real-time cell movements were also observed upon localized light stimulation. The established optogenetic method provides a novel spatiotemporal strategy for specific PIP3 visualization, which is beneficial to improve the understanding of PIP3 functions.

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Direct Evidence for the Action of Phosphatidylinositol (3,4,5)-Trisphosphate-Mediated Signal Transduction in the 2-Cell Mouse Embryo1

Cited by 32 publications

References 74 publications

Phosphatidylinositol 3-kinase signaling in mammalian preimplantation embryo development

Phosphatidylinositol 3-kinase signaling in mammalian preimplantation embryo development

Changing expression of chloride channels during preimplantation mouse development

Optogenetic Control of Phosphatidylinositol (3,4,5)‐Triphosphate Production by Light‐Sensitive Cryptochrome Proteins on the Plasma Membrane

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