An essential role for phospholipase D in the recruitment of vesicle amine transport protein-1 to membranes in human neutrophils

Faugaret, Delphine; Chouinard, François; Harbour, Danielle; Azreq, Mohammed-Amine El; Bourgoin, Sylvain G.

doi:10.1016/j.bcp.2010.09.014

Cited by 27 publications

(17 citation statements)

References 81 publications

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“…Even more interesting are hub genes from the LPS-downregulated module: albeit the function of the vesicle amine transport 1 protein encoded by VAT1 gene has not been fully described, it has been shown that this gene is expressed in human neutrophils and VAT1 protein is located peripherally in unstimulated neutrophils with a more granular pattern upon stimulation with a macrophage activator [95, 96]. Since our collection of PBMCs did not contain neutrophils, the function of VAT1 in PBMCs requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells

et al. 2017

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BackgroundLipopolysaccharide (endotoxin, LPS) is a strong inducer of the innate immune response. It is widespread in our environment, e.g. in house dust and contributes to asthma. Compared to humans, horses are even more sensitive to LPS. However, data on LPS effects on the equine transcriptome are very limited. Using RNA-seq we analysed LPS-induced differences in the gene expression in equine peripheral blood mononuclear cells at the gene and gene-network level in two half-sib families and one group of unrelated horses.Results24 h-LPS challenge of equine immune cells resulted in substantial changes in the transcriptomic profile (1,265 differentially expressed genes) showing partial overlap with human data. One of the half-sib families showed a specific response different from the other two groups of horses. We also identified co-expressed gene modules that clearly differentiated 24 h-LPS- from non-stimulated samples. These modules consisted of 934 highly interconnected genes and included genes involved in the immune response (e.g. IL6, CCL22, CXCL6, CXCL2), however, none of the top ten hub genes of the modules have been annotated as responsive to LPS in gene ontology.ConclusionsUsing weighted gene co-expression network analysis we identified ten co-expressed gene modules significantly regulated by in vitro stimulation with LPS. Apart from 47 genes (5%) all other genes highly interconnected within the most up- and down-regulated modules were also significantly differentially expressed (FDR < 0.05). The LPS-regulated module hub genes have not yet been described as having a role in the immune response to LPS (e.g. VAT1 and TTC25).Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3390-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells

et al. 2017

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“…Unlike voltage-gated sodium channels, VDACs have been implicated in the pathophysiology of neurotransmission pertaining to overactive bladder and dysuria (57). Another protein that was increased in abundance in the ASB and UTI proteomic profiles was synaptic vesicle membrane protein 1 (VAT-1), which was identified as a phosphatidic-acid-binding protein translocated to neutrophil membranes upon stimulation with N-formyl-methionyl-leucyl-phenylalanine (58). Interestingly, a VAT-1 ortholog in the marine ray (Torpedo californica) was described as a protein that is transported to cholinergic nerve terminals and abundant in synaptic vesicles.…”

Section: Discussionmentioning

confidence: 99%

Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria

et al. 2015

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bDifferential diagnosis of asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) is based on the presence of diverse symptoms, including fever (>38.5°C), rigors, malaise, lethargy, flank pain, hematuria, suprapubic discomfort, dysuria, and urgent or frequent urination. There is consensus in the medical community that ASB warrants antibiotic treatment only for patients undergoing urological procedures that lead to mucosal bleeding, catheterized individuals whose ASB persists for more than 48 h after catheter removal, and pregnant women. Pyuria is associated with UTI and implicates host immune responses via release of antibacterial effectors and phagocytosis of pathogens by neutrophils. Such responses are not sufficiently described for ASB. Metaproteomic methods were used here to identify the pathogens and evaluate molecular evidence of distinct immune responses in cases of ASB compared to UTI in elderly patients who were hospitalized upon injury. Neutrophil-driven inflammatory responses to invading bacteria were not discernible in most patients diagnosed with ASB compared to those with UTI. In contrast, proteomic urine analysis for trauma patients with no evidence of bacteriuria, including those who suffered mucosal injuries via urethral catheterization, rarely showed evidence of neutrophil infiltration. The same enzymes contributing to the synthesis of leukotrienes LTB 4 and LTC 4 , mediators of inflammation and pain, were found in the UTI and ASB cohorts. These data support the notion that the pathways mediating inflammation and pain in most elderly patients with ASB are not quantitatively different from those seen in most elderly patients with UTI and warrant larger clinical studies to assess whether a common antibiotic treatment strategy for elderly ASB and UTI patients is justified. U ncomplicated urinary tract infections (UTI) affect the health of approximately 150 million people worldwide and 7 million people in the United States annually; the majority of those affected are women (1). Ascending to the kidneys, UTIs lead to pyelonephritis, which is estimated to have an incidence of 12 cases per 10,000 women in the United States (2). Catheter-associated urinary tract infection (CAUTI), in particular, that seen following long-term catheterization, is characterized by biofilm formation on luminal and external urethral catheter surfaces and frequently causes nosocomial infections. CAUTIs are complicated UTIs because the rate of recurrence is higher and the effectiveness of short-term antibiotic treatment is decreased (3, 4). The incidence of CAUTIs, especially of CAUTIs contracted by elderly patients in long-term care centers and hospitals and by patients with spinal cord injuries and neurogenic bladders (3, 4), is estimated to be 0.9 to 1.5 million cases per year in the United States (1, 3). The infections are deemed potentially preventable complications of hospitalization by the Center of Medicare and Medicaid Services, and the associated costs are no longer reimbursed (3). Escherichia coli causes ...

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“…Furthermore, a newly published paper reported that PA also binds with Rac2 and Cdc42 in neutrophil cytosol using co-sedimentation with PA-containing vesicles and mass spectrometry, but the binding site in Rac2 with PA is still unknown (42). Another way in FIGURE 7.…”

Section: Discussionmentioning

confidence: 99%

Evidence for Two CRIB Domains in Phospholipase D2 (PLD2) That the Enzyme Uses to Specifically Bind to the Small GTPase Rac2

Peng

Henkels

Mahankali

et al. 2011

Journal of Biological Chemistry

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Phospholipase D (PLD) and small GTPases are vital to cell signaling. We report that the Rac2 and the PLD2 isoforms exist in the cell as a lipase-GTPase complex that enables the two proteins to elicit their respective functionalities. A strong association between the two molecules was demonstrated by co-immunoprecipitation and was confirmed in living cells by FRET with CFP-Rac2 and YFP-PLD2 fluorescent chimeras. We have identified the amino acids in PLD2 that define a specific binding site to Rac2. This site is composed of two CRIB (Cdc42-and Racinteractive binding) motifs that we have named "CRIB-1" and "CRIB-2" in and around the PH domain in PLD2. Deletion mutants PLD2-⌬CRIB-1/2 negate co-immunoprecipitation with Rac2 and diminish the FRET signal in living cells. The PLD2-Rac2 association was further confirmed in vitro using affinity-purified recombinant proteins. Binding was saturable with an apparent K d of 3 nM and was diminished with PLD2-⌬CRIB mutants. Furthermore, PLD2 bound more efficiently to Rac2-GTP than to Rac2-GDP or to a GDP-constitutive Rac2-N17 mutant. Increasing concentrations of recombinant Rac2 in vitro and in vivo during cell adhesion inhibit PLD2. Conversely, Rac2 activity is increased in the presence of PLD2-WT but not in PLD2-⌬CRIB. We propose that in activated cells PLD2 affects Rac2 in an initial positive feedback, but as Rac2-GTP accumulates in the cell, this constitutes a "termination signal" leading to PLD2 inactivation.

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An essential role for phospholipase D in the recruitment of vesicle amine transport protein-1 to membranes in human neutrophils

Cited by 27 publications

References 81 publications

LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells

LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells

Similar Neutrophil-Driven Inflammatory and Antibacterial Responses in Elderly Patients with Symptomatic and Asymptomatic Bacteriuria

Evidence for Two CRIB Domains in Phospholipase D2 (PLD2) That the Enzyme Uses to Specifically Bind to the Small GTPase Rac2

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