The role of LPA<sub>1</sub> in formation of synapses among cultured hippocampal neurons

Pilpel, Yair; Segal, Menahem

doi:10.1111/j.1471-4159.2006.03825.x

Cited by 41 publications

(41 citation statements)

References 42 publications

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“…However, it is clear that LPA 1 is normally a survival factor for neurons because apoptotic cell death occurs in embryonic and postnatal LPA 1 -null mouse brains [72]. In addition to neuronal survival/death, LPA and/or S1P signaling are linked to neuronal excitability [26,89–93], synapse formation [86,87], and synaptic transmission [14,94–96]. To date, a few pieces of this puzzle have been directly verified, but as yet unidentified receptor subtypes may mediate these responses.…”

Section: Biological Functions Of Lpa and S1p Receptors In Cns Cellmentioning

confidence: 99%

Lysophospholipids and their receptors in the central nervous system

Choi

Chun

2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

228

242

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Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), two of the best-studied lysophospholipids, are known to influence diverse biological events, including organismal development as well as function and pathogenesis within multiple organ systems. These functional roles are due to a family of at least 11 G protein-coupled receptors (GPCRs), named LPA1–6 and S1P1–5, which are widely distributed throughout the body and that activate multiple effector pathways initiated by a range of heterotrimeric G proteins including Gi/o, G12/13, Gq and Gs, with actual activation dependent on receptor subtypes. In the central nervous system (CNS), a major locus for these signaling pathways, LPA and S1P have been shown to influence myriad responses in neurons and glial cell types through their cognate receptors. These receptor-mediated activities can contribute to disease pathogenesis and have therapeutic relevance to human CNS disorders as demonstrated for multiple sclerosis (MS) and possibly others that include congenital hydrocephalus, ischemic stroke, neurotrauma, neuropsychiatric disorders, developmental disorders, seizures, hearing loss, and Sandhoff disease, based upon the experimental literature. In particular, FTY720 (fingolimod, Gilenya, Novartis Pharma, AG) that becomes an analog of S1P upon phosphorylation, was approved by the FDA in 2010 as a first oral treatment for MS, validating this class of receptors as medicinal targets. This review will provide an overview and update on the biological functions of LPA and S1P signaling in the CNS, with a focus on results from studies using genetic null mutants for LPA and S1P receptors. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.

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Section: Biological Functions Of Lpa and S1p Receptors In Cns Cellmentioning

confidence: 99%

Lysophospholipids and their receptors in the central nervous system

Choi

Chun

2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

228

242

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“…on the solubility of this moiety [36]). Experiments in the presence of A23187, LPA, or PMA were also carried out in the absence of extracellular Ca 2+ by adding 2 mM EGTA.…”

Section: +mentioning

confidence: 99%

Characterization of Microvesicles Released from Human Red Blood Cells

Nguyen

Wesseling

et al. 2016

Cell Physiol Biochem

105

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Background/Aims: Extracellular vesicles (EVs) are spherical fragments of cell membrane released from various cell types under physiological as well as pathological conditions. Based on their size and origin, EVs are classified as exosome, microvesicles (MVs) and apoptotic bodies. Recently, the release of MVs from human red blood cells (RBCs) under different conditions has been reported. MVs are released by outward budding and fission of the plasma membrane. However, the outward budding process itself, the release of MVs and the physical properties of these MVs have not been well investigated. The aim of this study is to investigate the formation process, isolation and characterization of MVs released from RBCs under conditions of stimulating Ca²⁺ uptake and activation of protein kinase C. Methods: Experiments were performed based on single cell fluorescence imaging, fluorescence activated cell sorter/flow cytometer (FACS), scanning electron microscopy (SEM), atomic force microscopy (AFM) and dynamic light scattering (DLS). The released MVs were collected by differential centrifugation and characterized in both their size and zeta potential. Results: Treatment of RBCs with 4-bromo-A23187 (positive control), lysophosphatidic acid (LPA), or phorbol-12 myristate-13 acetate (PMA) in the presence of 2 mM extracellular Ca²⁺ led to an alteration of cell volume and cell morphology. In stimulated RBCs, exposure of phosphatidylserine (PS) and formation of MVs were observed by using annexin V-FITC. The shedding of MVs was also observed in the case of PMA treatment in the absence of Ca²⁺, especially under the transmitted bright field illumination. By using SEM, AFM and DLS the morphology and size of stimulated RBCs, MVs were characterized. The sizes of the two populations of MVs were 205.8 ± 51.4 nm and 125.6 ± 31.4 nm, respectively. Adhesion of stimulated RBCs and MVs was observed. The zeta potential of MVs was determined in the range from - 40 mV to - 10 mV depended on the solutions and buffers used. Conclusion: An increase of intracellular Ca²⁺ or an activation of protein kinase C leads to the formation and release of MVs in human RBCs.

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“…A number of studies have shown that LPAR signaling plays a critical role during early development stages, including the regulation of synapse formation and the morphology of cortical and hippocampal neurons (Dubin et al 2010;Estivill-Torrús et al 2008;Fukushima et al 2000;Pilpel and Segal 2006). Even though the expression level of LPARs is known to decrease with age Choi et al 2008;Chun 2005;Noguchi et al 2009), LPA-mediated signaling seems to play important roles in aged animals, as well.…”

mentioning

confidence: 99%

Synaptic enhancement induced by gintonin via lysophosphatidic acid receptor activation in central synapses

Park

Kim

Rhee

et al. 2015

Journal of Neurophysiology

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Park H, Kim S, Rhee J, Kim HJ, Han JS, Nah SY, Chung C. Synaptic enhancement induced by gintonin via lysophosphatidic acid receptor activation in central synapses. J Neurophysiol 113: 1493-1500, 2015. First published December 10, 2014 doi:10.1152/jn.00667.2014 is one of the well-characterized, ubiquitous phospholipid molecules. LPA exerts its effect by activating G protein-coupled receptors known as LPA receptors (LPARs). So far, LPAR signaling has been critically implicated during early development stages, including the regulation of synapse formation and the morphology of cortical and hippocampal neurons. In adult brains, LPARs seem to participate in cognitive as well as emotional learning and memory. Recent studies using LPAR1-deficient mice reported impaired performances in a number of behavioral tasks, including the hippocampus-dependent spatial memory and fear conditioning tests. Nevertheless, the effect of LPAR activation in the synaptic transmission of central synapses after the completion of embryonic development has not been investigated. In this study, we took advantage of a novel extracellular agonist for LPARs called gintonin to activate LPARs in adult brain systems. Gintonin, a recently identified active ingredient in ginseng, has been shown to activate LPARs and mobilize Ca 2ϩ in an artificial cell system. We found that the activation of LPARs by application of gintonin acutely enhanced both excitatory and inhibitory transmission in central synapses, albeit through tentatively distinct mechanisms. Gintonin-mediated LPAR activation primarily resulted in synaptic enhancement and an increase in neuronal excitability in a phospholipase C-dependent manner. Our findings suggest that LPARs are able to directly potentiate synaptic transmission in central synapses when stimulated exogenously. Therefore, LPARs could serve as a useful target to modulate synaptic activity under pathological conditions, including neurodegenerative diseases. synaptic potentiation; lysophosphatidic acid receptor; ginseng; gintonin LYSOPHOSPHATIDIC ACID (LPA) is one of the well-characterized, ubiquitous phospholipids and exerts its effect by activating G protein-coupled receptors known as LPA receptors 1-5 (LPAR1-LPAR5; Choi et al. 2010). A number of studies have shown that LPAR signaling plays a critical role during early development stages, including the regulation of synapse formation and the morphology of cortical and hippocampal neurons (Dubin et al.

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The role of LPA₁ in formation of synapses among cultured hippocampal neurons

Cited by 41 publications

References 42 publications

Lysophospholipids and their receptors in the central nervous system

Lysophospholipids and their receptors in the central nervous system

Characterization of Microvesicles Released from Human Red Blood Cells

Synaptic enhancement induced by gintonin via lysophosphatidic acid receptor activation in central synapses

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The role of LPA1 in formation of synapses among cultured hippocampal neurons

Cited by 41 publications

References 42 publications

Lysophospholipids and their receptors in the central nervous system

Lysophospholipids and their receptors in the central nervous system

Characterization of Microvesicles Released from Human Red Blood Cells

Synaptic enhancement induced by gintonin via lysophosphatidic acid receptor activation in central synapses

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The role of LPA₁ in formation of synapses among cultured hippocampal neurons