Systematic Analysis of γ-Aminobutyric Acid (GABA) Metabolism and Function in the Social Amoeba Dictyostelium discoideum

Wu, Yuantai; Janetopoulos, Christopher

doi:10.1074/jbc.m112.427047

Cited by 14 publications

(14 citation statements)

References 44 publications

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“…4 D). Dictyostelium has a GABA signalling system, which is active during development ( Taniura et al, 2006 ; Anjard and Loomis, 2006 ; Wu and Janetopoulos, 2013 ) and we found that GABA and L-glutamate both evoke a cytoplasmic calcium signal from aggregation-competent cells, although this was erratic ( Fig. 4 B,C).…”

Section: Resultsmentioning

confidence: 69%

A polycycstin-type transient receptor potential (Trp) channel that is activated by ATP

Traynor

Kay

2016

Biology Open

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ATP and ADP are ancient extra-cellular signalling molecules that in Dictyostelium amoebae cause rapid, transient increases in cytosolic calcium due to an influx through the plasma membrane. This response is independent of hetero-trimeric G-proteins, the putative IP3 receptor IplA and all P2X channels. We show, unexpectedly, that it is abolished in mutants of the polycystin-type transient receptor potential channel, TrpP. Responses to the chemoattractants cyclic-AMP and folic acid are unaffected in TrpP mutants. We report that the DIF morphogens, cyclic-di-GMP, GABA, glutamate and adenosine all induce strong cytoplasmic calcium responses, likewise independently of TrpP. Thus, TrpP is dedicated to purinergic signalling. ATP treatment causes cell blebbing within seconds but this does not require TrpP, implicating a separate purinergic receptor. We could detect no effect of ATP on chemotaxis and TrpP mutants grow, chemotax and develop almost normally in standard conditions. No gating ligand is known for the human homologue of TrpP, polycystin-2, which causes polycystic kidney disease. Our results now show that TrpP mediates purinergic signalling in Dictyostelium and is directly or indirectly gated by ATP.

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Section: Resultsmentioning

confidence: 69%

A polycycstin-type transient receptor potential (Trp) channel that is activated by ATP

Traynor

Kay

2016

Biology Open

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“…discoideum genome encodes 14 class C GPCRs, including fAR1, that contain extracellular VFT domains. Bioinformatics analysis suggested that the VFT domain of these members are evolutionarily closer to bacterial PBPs and eukaryotic GABA B Rs family than to other class C GPCRs [ 47 , 48 ], constituting the prototype of class C GPCRs with a variety of physiological functions [ 49 ]. Interestingly, bacterial PBPs bind various ligands, while most mammalian class C GPCRs expressed in the central nerve system bind only one natural ligand, implying that during evolution, VFT domains of class C GPCRs underwent partial loss of function, such as the ability to bind various ligands [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

A G-protein-coupled chemoattractant receptor recognizes lipopolysaccharide for bacterial phagocytosis

et al. 2018

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Phagocytes locate microorganisms via chemotaxis and then consume them using phagocytosis. Dictyostelium amoebas are stereotypical phagocytes that prey on diverse bacteria using both processes. However, as typical phagocytic receptors, such as complement receptors or Fcγ receptors, have not been found in Dictyostelium, it remains mysterious how these cells recognize bacteria. Here, we show that a single G-protein-coupled receptor (GPCR), folic acid receptor 1 (fAR1), simultaneously recognizes the chemoattractant folate and the phagocytic cue lipopolysaccharide (LPS), a major component of bacterial surfaces. Cells lacking fAR1 or its cognate G-proteins are defective in chemotaxis toward folate and phagocytosis of Klebsiella aerogenes. Computational simulations combined with experiments show that responses associated with chemotaxis can also promote engulfment of particles coated with chemoattractants. Finally, the extracellular Venus-Flytrap (VFT) domain of fAR1 acts as the binding site for both folate and LPS. Thus, fAR1 represents a new member of the pattern recognition receptors (PRRs) and mediates signaling from both bacterial surfaces and diffusible chemoattractants to reorganize actin for chemotaxis and phagocytosis.

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“…According to reports, inclusion body hepatitis can reduce the level of Bu‐Ia + B lymphocyte in chicken (Wang and Wang, ), implying that the decline of Bu‐Ia + B lymphocytes under HS may be related to inflammatory response. The promotion of B lymphocyte development by GABA under HS is possibly achieved by enhancing the metabolism and providing a large amount of energy substances such as glutamate (Akcay et al., ; Wu and Janetopoulos, ).…”

Section: Discussionmentioning

confidence: 99%

The protective effect of γ‐aminobutyric acid on the development of immune function in chickens under heat stress

Jia

Chen

2015

Animal Physiology Nutrition

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This study aimed to investigate the protective effect of γ-aminobutyric acid (GABA) on the development of immune function in chicks under heat stress (HS). One-day-old male Wenchang chicks were randomly divided into control (CK), HS and GABA+HS groups. The GABA+HS group was fed with 0.2 ml GABA solution (50 mg/kg) daily by oral gavage. The HS and GABA+HS groups were placed in 40 ± 0.5 °C environment for 2 h heat treatment from 13:00 each day. Blood samples were routinely taken at 14, 21, 28, 35 and 42 days respectively, and the contents of T and B lymphocyte subsets in the blood and tissue were analysed by flow cytometry after FITC/PE double staining; the plasma levels of interleukin (IL)-2, immunoglobulin (Ig)A, IgG and IgM were determined using ELISA. The thymus and the bursa of fabricius were also collected to analyse for organ index and observe for the changes in tissue microstructure. In addition, the chicks received primary and secondary immunizations with attenuated Newcastle disease (ND) vaccine (LaSota strain) at 7 and 28 days respectively; conventional hemagglutination inhibition (HI) assay was performed to monitor the titre changes in plasma antibody against ND virus in the birds. Our results indicated that the indices of both thymus and bursa of fabricius, the intactness of tissue structure and development, the plasma levels of IL-2, IgA, IgG and IgM, the titres of ND antibody, and the levels of B and T lymphocyte subsets in HS group were all significantly lower than those in CK group (p < 0.05). However, all above indices were significantly improved in GABA+HS group compared with those in HS group (p < 0.05). These results demonstrated that while HS seriously affected the development of immune function in Wenchang chicks, GABA effectively alleviated the damages of HS to the development of immune function in chicks.

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Systematic Analysis of γ-Aminobutyric Acid (GABA) Metabolism and Function in the Social Amoeba Dictyostelium discoideum

Cited by 14 publications

References 44 publications

A polycycstin-type transient receptor potential (Trp) channel that is activated by ATP

A polycycstin-type transient receptor potential (Trp) channel that is activated by ATP

A G-protein-coupled chemoattractant receptor recognizes lipopolysaccharide for bacterial phagocytosis

The protective effect of γ‐aminobutyric acid on the development of immune function in chickens under heat stress

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