Recognition of Bacterial Signal Peptides by Mammalian Formyl Peptide Receptors

Bufe, Bernd; Schumann, Timo; Kappl, Reinhard; Bogeski, Ivan; Kummerow, Carsten; Podgórska, Marta; Smola, Sigrun; Hoth, Markus; Zufall, Frank

doi:10.1074/jbc.m114.626747

Cited by 87 publications

(129 citation statements)

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“…Our detection of Fpr3 protein in neutrophils by two selective antibodies, the colocalization with the neutrophil marker Ly6G, a clear verification of Fpr3 expression in RT-PCR experiments, and an inducible increase of Fpr3 protein production after LPS exposure all provided clear evidence for the presence of Fpr3 in specific immune cells. These observations thus argue for an orthologous function of Fpr3 in human and mouse immune cells, a result that should help to explain the obvious functional similarities in human and mouse Fpr3 ligand detection (27,32,33).…”

Section: Discussionmentioning

confidence: 84%

“…We previously identified a set of formylated bacterial signal peptides as natural agonists for this receptor (32), and we demonstrated that human FPR3 responds to a similar ligand spectrum (32). These in vitro studies, together with the close sequence homology of both receptors (32,33), indicate that human and mouse Fpr3 could share orthologous roles in pathogen detection. However, the known expression patterns of both receptors seem to contrast with this idea.…”

mentioning

confidence: 73%

“…Second, peptide motifs that activate Fpr3 are found far more frequently in bacteria than in other organisms (33). Third, Fpr1 and Fpr2 seem to have evolved as pathogen recognition receptors that recognize structurally conserved export motifs of bacterial signal peptides (32). Fpr3 fits into this mechanistic concept because it is also a bacterial signal peptide receptor, although with a more specific detection range (32).…”

Section: Discussionmentioning

confidence: 99%

“…Calcium Imaging-Cell population responses of transfected HEK293T cells (ϳ50,000 cells per well) were recorded using a fluorometric imaging plate reader system (Molecular Devices) as described previously (32,33,41). Briefly, 48 h after transfection, cells were incubated with 2 M Fluo-4 AM (Molecular Probes) and 50 M probenicid (Sigma) for 2 h at room temperature in a C1 bath solution (130 mM NaCl, 10 mM HEPES, 5 mM KCl, 2 mM CaCl 2 , 5 mM glucose ( pH 7.4)).…”

Section: Methodsmentioning

confidence: 99%

“…To test this, we used an established in vitro calcium imaging assay (33). We first performed calcium imaging in HEK cells transiently transfected with either Fpr3⌬424 -435 or Fpr3 wt and recorded calcium responses to 30 M W-peptide, a potent Fpr3 agonist (32,33). 177/475 cells (37%) transfected with Fpr3 wt were robustly activated by the W-peptide, but none of the analyzed 686 cells transfected with Fpr3⌬424 -435 responded to this stimulus (Fig.…”

Section: Fpr3 Protein Expression Occurs In a Strain-specific Manner-mentioning

confidence: 99%

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Strain-specific Loss of Formyl Peptide Receptor 3 in the Murine Vomeronasal and Immune Systems

Stempel¹,

Jung

Pérez-Gómez³

et al. 2016

Journal of Biological Chemistry

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Social animals benefit from sharing information that promotes fitness and survival (1-3). In rodents, there is extensive evidence that the detection of chemosensory cues emitted by other individuals is a fundamental feature of social recognition and a prerequisite for a wide range of social behaviors (4 -6).For example, rodents use such chemical signals to distinguish between parasitized individuals, recognize infected conspecifics, and avoid and display aversive responses to infected individuals (7-9). Defining the cellular and molecular mechanisms and neural circuits underlying the detection of infection-and illness-associated states is not only crucial for understanding the sensing of health status in animals but also for advancing our knowledge of disease-related odors and diagnostic olfactory biomarkers in humans (10, 11).The vomeronasal organ (VNO) 4 is an olfactory substructure of the mammalian nose that is essential for social recognition and chemical communication (12). The VNO houses vomeronasal sensory neurons (VSNs), specialized nerve cells that detect a wide range of volatile and non-volatile molecular cues, including pheromones and predator odors (13-15). Among these cues are major histocompatibility complex class I binding peptides (antigens) and other small urinary peptides (16 -18) thus providing initial support for an evolutionary link between recognition mechanisms in immune cells and subsets of VSNs (14, 19). More recently, clear evidence has emerged that the VNO plays an important role in mediating sick conspecific avoidance and thus seems to function as a sensor of infection (20), but the underlying cellular and molecular basis for this function remains unclear. VSNs are characterized by the expression of large families of G protein-coupled receptors, vomeronasal type 1 receptors (Vmn1r) expressed in the apical vomeronasal layer and vomeronasal type 2 receptor (Vmn2r) that function together with non-classical class I major histocompatibility complex receptors of the H2-Mv subtype in the basal layer (21, 22). An important development has been the identification of a third family of G protein-coupled receptors expressed in subsets of VSNs as follows: the formyl peptide receptors (Fprs) (23,24). Fprs are primarily known from the innate immune system where they are involved in chemoattraction of phagocytic immune cells to sites of infection mediating host defense against invading microorganisms (25-28). Fprs detect a wide range of inflammation markers as well as bacterial and mitochondrial peptides (25-28), and consistent with the results from immune cells, some of these ligands have also been shown to activate specific VSNs (23,29). Hence, members of the Fpr family are currently prime candidates for mediating VNO pathogen sensing, although it cannot be ruled out that

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Section: Discussionmentioning

confidence: 84%

mentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Fpr3 Protein Expression Occurs In a Strain-specific Manner-mentioning

confidence: 99%

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Strain-specific Loss of Formyl Peptide Receptor 3 in the Murine Vomeronasal and Immune Systems

Stempel¹,

Jung

Pérez-Gómez³

et al. 2016

Journal of Biological Chemistry

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An updated synthesis of and outstanding questions in the olfactory and vomeronasal systems in bats: Genetics asks questions only anatomy can answer

Yohe,

Krell

2023

The Anatomical Record

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The extensive diversity observed in bat nasal chemosensory systems has been well‐documented at the histological level. Understanding how this diversity evolved and developing hypotheses as to why particular patterns exist require a phylogenetic perspective, which was first outlined in the work of anatomist Kunwar Bhatnagar. With the onset of genetics and genomics, it might be assumed that the puzzling patterns observed in the morphological data have been clarified. However, there is still a widespread mismatch of genetic and morphological correlations among bat chemosensory systems. Novel genomic evidence has set up new avenues to explore that demand more evidence from anatomical structures. Here, we outline the progress that has been made in both morphological and molecular studies on the olfactory and vomeronasal systems in bats since the work of Bhatnagar. Genomic data of olfactory and vomeronasal receptors demonstrate the strong need for further morphological sampling, with a particular focus on receiving brain regions, glands, and ducts.

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Anti‐interleukin‐17A and anti‐interleukin‐23 antibodies may be effective against Alzheimer's disease: Role of neutrophils in the pathogenesis

Katayama¹

2019

Brain and Behavior

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Alzheimer's disease (AD), a neurodegenerative disease involving loss of cognitive function and memory, affects more than 35 million people worldwide (Querfurth & LaFerla, 2010). However, despite the remarkable progress achieved in AD research (Sanabria-Castro, Alvarado-Echeverria, & Monge-Bonilla, 2017), its exact pathogenesis is not fully understood and effective therapies for AD do not currently exist. During my research on the pathogenesis of psoriasis and the therapeutic mechanisms of anti-interleukin-17A (anti-IL-17A) (Appendix) and anti-interleukin-23 (anti-IL-23) antibodies on psoriasis (Katayama, 2018), I considered whether these antibodies would also be effective against AD.

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Recognition of Bacterial Signal Peptides by Mammalian Formyl Peptide Receptors

Cited by 87 publications

References 58 publications

Strain-specific Loss of Formyl Peptide Receptor 3 in the Murine Vomeronasal and Immune Systems

Strain-specific Loss of Formyl Peptide Receptor 3 in the Murine Vomeronasal and Immune Systems

An updated synthesis of and outstanding questions in the olfactory and vomeronasal systems in bats: Genetics asks questions only anatomy can answer

Anti‐interleukin‐17A and anti‐interleukin‐23 antibodies may be effective against Alzheimer's disease: Role of neutrophils in the pathogenesis

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