UniProt release 15.7

Formyl peptide receptors: the missing link between olfaction and immune system

Olfaction plays a major role in the social life of many animals, including mammals, and in their interaction with the environment. In most mammals, the olfactory system has 2 components. 1) The main system is located in the nasal olfactory epithelium (OE) and detects environmental odors, such as those emitted by food and predators. 2) The accessory system is located in the vomeronasal organ (VNO) and detects pheromones. The VNO is linked directly to the brain's emotional centers, such as amygdala and hypothalamus, which control basic drives, hormonal levels, and instinctive behaviours, while OE signals are sent to higher cortical and limbic areas. As a result, signals conveyed by VNO trigger immediate reactions.

Recently, a new family of vomeronasal chemoreceptors has been identified, termed the formyl peptide receptors. In the mouse, 5 formyl peptide receptors are expressed in VNO: Fpr-rs1 (also called Fpr3), Fpr-rs3, Fpr-rs4, Fpr-rs6, and Fpr-rs7. Fpr-rs1, as well as another member of the family, Fpr1, have been previously shown to be expressed within granulocytes, monocytes and macrophages of the immune system. Their ligands include N-formyl-methionyl peptides (fMLP) released by Gram-negative bacteria, HIV-derived peptides, the antimicrobial peptide CRAMP, lipoxin A4, etc. Upon ligand recognition, these chemoreceptors stimulate chemotaxis of the immune cells to the site of infection or tissue damage.

Interestingly, VNO Fpr-rs respond to various degrees to most of the stimuli that affect their relatives in the immune system. Sensitivity to disease/inflammation-related ligands presents major advantages, such as the detection of spoiled food. Although Fpr-rs agonists are mostly produced in tissues and serum after inflammation, they are also present in some bodily fluids, such as urine. This could allow their olfactory detection by conspecifics, leading to the rapid isolation of sick individuals and hence minimizing the risk of disease spreading within a community.

As of this release, all 5 VNO Fpr-rs are annotated and available from UniProtKB/Swiss-Prot.

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Cross-references to STRING

Cross-references have been added to STRING, a resource of known and predicted protein-protein interactions, which quantitatively integrates interaction data from four sources for a large number of organisms, and transfers information between these organisms where applicable.

STRING is available at http://string-db.org/.

The format of the explicit links in the flat file is:

P17735:
DR   STRING; P17735; -.

Changes in subcellular location controlled vocabulary

New subcellular locations:

• Host nucleus outer membrane
• Host smooth endoplasmic reticulum
• Host smooth endoplasmic reticulum membrane