Formyl Peptide Receptors from Immune and Vomeronasal System Exhibit Distinct Agonist Properties

Bufe, Bernd; Schumann, Timo; Zufall, Frank

doi:10.1074/jbc.m112.375774

Cited by 50 publications

(68 citation statements)

References 43 publications

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“…Cloning of Murine Fpr Genes-Fpr1, Fpr2, Fpr3 (previously known as Fpr-rs1), Fpr-rs3, Fpr-rs4, Fpr-rs6, and Fpr-rs7 were amplified from C57BL/6NJ mice by PCR and subcloned into pcDNA3.1 (ϩ) (Thermo Scientific) as described previously (33). Fpr3⌬424 -435 is identical to Fpr3 except for a 12-nucleotide in-frame deletion occurring from base pair 424 to 435.…”

Section: Methodsmentioning

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%

“…Fpr3⌬424 -435 is identical to Fpr3 except for a 12-nucleotide in-frame deletion occurring from base pair 424 to 435. Fpr3⌬424 -435 was amplified and subcloned into pcDNA3.1 (ϩ) from genomic DNA of 129X1/Sv mice using the Phusion HF Master Mix (Thermo Scientific) according to the manufacturer's protocol with the primer and reaction conditions as described (33). The Fpr3⌬424 -435 fusion construct was obtained by in-frame subcloning of an Fpr3 PCR product from genomic DNA of 129X1/Sv into a modified pcDNA5/FRT/TO vector containing an N-terminal rhodopsin epitope (Rho tag) and a C-terminal herpes simplex virus epitope (HSV tag).…”

Section: Methodsmentioning

confidence: 99%

“…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.…”

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confidence: 98%

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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: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 98%

See 2 more Smart Citations

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

Self Cite

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“…In situ experiments have shown that VSNs are also activated by formylated peptides and various antimicrobial/inflammation-linked compounds 25,42 . Moreover, heterologously expressed FPR-rs proteins share agonist spectra with FPRs expressed in the immune system, indicating a potential role as detectors for sickness in conspecifics or spoiled food sources 25 (see reference 43 ). …”

Section: Introductionmentioning

confidence: 99%

In-depth Physiological Analysis of Defined Cell Populations in Acute Tissue Slices of the Mouse Vomeronasal Organ

Ackels

Drose

Spehr

2016

JoVE

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In most mammals, the vomeronasal organ (VNO) is a chemosensory structure that detects both hetero-and conspecific social cues. Vomeronasal sensory neurons (VSNs) express a specific type of G protein-coupled receptor (GPCR) from at least three different chemoreceptor gene families allowing sensitive and specific detection of chemosensory cues. These families comprise the V1r and V2r gene families as well as the formyl peptide receptor (FPR)-related sequence (Fpr-rs) family of putative chemoreceptor genes. In order to understand the physiology of vomeronasal receptor-ligand interactions and downstream signaling, it is essential to identify the biophysical properties inherent to each specific class of VSNs.The physiological approach described here allows identification and in-depth analysis of a defined population of sensory neurons using a transgenic mouse line (Fpr-rs3-i-Venus). The use of this protocol, however, is not restricted to this specific line and thus can easily be extended to other genetically modified lines or wild type animals.

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The Vomeronasal Organ

Stowers

Spehr

2015

Handbook of Olfaction and Gustation

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Formyl Peptide Receptors from Immune and Vomeronasal System Exhibit Distinct Agonist Properties

Cited by 50 publications

References 43 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

In-depth Physiological Analysis of Defined Cell Populations in Acute Tissue Slices of the Mouse Vomeronasal Organ

The Vomeronasal Organ

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