Nouveaux rôles physiopathologiques pour le récepteur PLA2R1 dans le cancer et la glomérulonéphrite extramembraneuse

Girard, Christophe A.; Seitz-Polski, Barbara; Dolla, Guillaume; Augert, Arnaud; Vindrieux, David; Bernard, David; Lambeau, Gérard

doi:10.1051/medsci/20143005014

Cited by 4 publications

(3 citation statements)

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“…The second hypothesis proposes that the receptor could activate a cellular signaling pathway allowing an adequate answer of the cell to its changing environment [ 34 , 35 ]. However, besides the role of some intracellular motifs involved in its internalization properties, the exact downstream effectors of PLA2R1, which are the binding partners and the cellular signaling pathways that would be activated upon ligand binding, remain enigmatic [ 36 , 37 ]. For instance, PLA2R1 has been reported to be present in different immune cell types as mast cells, and neutrophils and may be involved in some sPLA 2 -induced effects [ 38 , 39 , 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Treatment of Mouse Sperm with a Non-Catalytic Mutant of PLA2G10 Reveals That PLA2G10 Improves In Vitro Fertilization through Both Its Enzymatic Activity and as Ligand of PLA2R1

Nahed

Dhellemmes

Payré

et al. 2022

IJMS

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The group X secreted phospholipase A2 (PLA2G10) is present at high levels in mouse sperm acrosome. The enzyme is secreted during capacitation and amplifies the acrosome reaction and its own secretion via an autocrine loop. PLA2G10 also improves the rate of fertilization. In in vitro fertilization (IVF) experiments, sperm from Pla2g10-deficient mice produces fewer two-cell embryos, and the absence of PLA2G10 is rescued by adding recombinant enzymes. Moreover, wild-type (WT) sperm treated with recombinant PLA2G10 produces more two-cell embryos. The effects of PLA2G10 on mouse fertility are inhibited by sPLA2 inhibitors and rescued by products of the enzymatic reaction such as free fatty acids, suggesting a role of catalytic activity. However, PLA2G10 also binds to mouse PLA2R1, which may play a role in fertility. To determine the relative contribution of enzymatic activity and PLA2R1 binding in the profertility effect of PLA2G10, we tested H48Q-PLA2G10, a catalytically-inactive mutant of PLA2G10 with low enzymatic activity but high binding properties to PLA2R1. Its effect was tested in various mouse strains, including Pla2r1-deficient mice. H48Q-PLA2G10 did not trigger the acrosome reaction but was as potent as WT-PLA2G10 to improve IVF in inbred C57Bl/6 mice; however, this was not the case in OF1 outbred mice. Using gametes from these mouse strains, the effect of H48Q-PLA2G10 appeared dependent on both spermatozoa and oocytes. Moreover, sperm from C57Bl/6 Pla2r1-deficient mice were less fertile and lowered the profertility effects of H48Q-PLA2G10, which were completely suppressed when sperm and oocytes were collected from Pla2r1-deficient mice. Conversely, the effect of WT-PLA2G10 was not or less sensitive to the absence of PLA2R1, suggesting that the effect of PLA2G10 is polymodal and complex, acting both as an enzyme and a ligand of PLA2R1. This study shows that the action of PLA2G10 on gametes is complex and can simultaneously activate the catalytic pathway and the PLA2R1-dependent receptor pathway. This work also shows for the first time that PLA2G10 binding to gametes’ PLA2R1 participates in fertilization optimization.

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Section: Discussionmentioning

confidence: 99%

Treatment of Mouse Sperm with a Non-Catalytic Mutant of PLA2G10 Reveals That PLA2G10 Improves In Vitro Fertilization through Both Its Enzymatic Activity and as Ligand of PLA2R1

Nahed

Dhellemmes

Payré

et al. 2022

IJMS

Self Cite

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“…L'hydrolyse par la Lp-PLA2 produit essentiellement de la lysophosphatidylcholine, qui induit le recrutement monocytaire et la dégranulation des polynucléaires neutrophiles [8]. Les sPLA2 sont également produites par les cellules de l'immunité naturelle (monocytes/macrophages) et adaptative (lymphocytes T) [9], et par les cellules de la paroi vasculaire [38] ( §). Les sPLA2 des groupes IIA (GIIA), III (GIII) et V (GV) ont été identifiées dans les plaques d'athérosclérose chez la souris et chez l'homme [10].…”

Section: Lp-pla2 Et Risque Cardiovasculaireunclassified

Lp-PLA2 et sPLA2

2014

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“…Les principales manifestations du syndrome néphrotique incluent protéinurie (> 3 g/24h), hypoalbuminémie, oedèmes, hyperlipidémie (hypercholestérolémie et hypertriglycéridémie), et lipidurie. La néphropathie diabétique (ND), la néphropathie à lésions glomérulaires minimes (LGM), la glomérulosclérose segmentaire et focale (FSGS), et la glomérulopathie extra-membraneuse (GEM) [11], maladies classées parmi les néphropathies glomérulaires [1], sont les causes majeures du syndrome néphrotique. Malgré l'identification de protéines structurelles clés pouvant contribuer à des défauts de la filtration rénale, la plupart des mécanismes à l'origine du syndrome néphrotique ne sont toujours pas élucidés.…”

Section: Définition Du Syndrome Néphrotiqueunclassified

Implication d’Angptl4 dans le syndrome néphrotique

Macé

Clement

2014

Med Sci (Paris)

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Nouveaux rôles physiopathologiques pour le récepteur PLA2R1 dans le cancer et la glomérulonéphrite extramembraneuse

Cited by 4 publications

References 44 publications

Treatment of Mouse Sperm with a Non-Catalytic Mutant of PLA2G10 Reveals That PLA2G10 Improves In Vitro Fertilization through Both Its Enzymatic Activity and as Ligand of PLA2R1

Treatment of Mouse Sperm with a Non-Catalytic Mutant of PLA2G10 Reveals That PLA2G10 Improves In Vitro Fertilization through Both Its Enzymatic Activity and as Ligand of PLA2R1

Lp-PLA2 et sPLA2

Implication d’Angptl4 dans le syndrome néphrotique

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