From immune to olfactory expression: neofunctionalization of formyl peptide receptors

Boillat, Madlaina; Carleton, Alan; Rodríguez, Iván

doi:10.1007/s00441-020-03393-5

Cited by 12 publications

(9 citation statements)

References 42 publications

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“…Intriguingly, one of the molecules found to be differentially expressed in the lungs of COVID-19 patients is the formyl peptide receptor, FPR2/FPRL1/ALX 34 , a G protein-coupled receptor and homolog of the Fpr family of vomeronasal receptors in mice. While FPR2 and its mouse equivalent are not considered to act as vomeronasal receptors 35,36 , it is active both in the brain and in immune cells, and is best known for its proin ammatory or in ammation-resolving actions depending on the activating ligand and signaling pathway triggered 37 . It also binds a variety of viral peptides and regulates viral RNA replication [38][39][40] .…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 infects human GnRH neurons and tanycytes, disrupting hypothalamic-pituitary hormonal axes

Sauvé¹,

Nampoothiri²,

Fernandois³

et al. 2021

Preprint

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Neuroinvasion by SARS-CoV-2 is now accepted. To investigate whether low testosterone levels observed in men with severe COVID-19 could be of central origin, we retrospectively analyzed blood samples from 60 male intensive-care patients and explored SARS-CoV-2 brain entry using animal and cellular models as well as adult COVID-19 patient and fetal human brains. Most hypotestosteronemic patients displayed hypogonadotropic hypogonadism or abnormal hypothalamic-pituitary-gonadal axis regulation. Neurons producing gonadotropin-releasing hormone (GnRH), the master molecule controlling fertility, expressed angiotensin-converting enzyme 2 and neuropilin-1, two host-cell factors mediating infection, and were infected and dying in all COVID-19 patient brains. Tanycytes - hypothalamic glia that regulate GnRH secretion - were also infected. Additionally, human fetal olfactory and vomeronasal epithelia, from which GnRH neurons arise, richly expressed both the above host-cell susceptibility factors and formyl peptide receptor 2, a putative vomeronasal receptor that also appeared involved in SARS-CoV-2 pathogenesis in humans and mice. Finally, a fetal human GnRH cell line expressing all these receptors could be infected by a SARS-CoV-2-like pseudovirus. Together, our findings suggest that GnRH neurons, which may be implicated in brain development and aging in addition to reproduction, are particularly vulnerable to SARS-CoV-2 in both adults and fetuses/newborns, with potentially devastating long-term consequences.

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Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 infects human GnRH neurons and tanycytes, disrupting hypothalamic-pituitary hormonal axes

Sauvé¹,

Nampoothiri²,

Fernandois³

et al. 2021

Preprint

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“…TAARs are also expressed in receptor neurons of the GG (157). Apart from a particular vomeronasal receptor (V2R83) that is expressed in the ciliated receptor neurons of the GG (34,153), all vomeronasal receptors of type 1 and type 2 (V1Rs and V2Rs) and all formyl peptide receptors (FPRs) are exclusively expressed in microvillous receptor neurons (25,35,(158)(159)(160). Differently from the above, the members of the membrane-spanning 4A receptors (MS4As) are coexpressed with GC-D in receptor neurons of the necklace subsystem that characteristically have neither cilia nor microvilli (25,38,149,150).…”

Section: Olfactory Ensheathing Cellsmentioning

confidence: 99%

“…After the discovery of the first vertebrate odorant receptor gene family, whose members have been generically named OR-type receptors (151), five additional receptor gene families have been discovered (see FIGURE 6): 1) two families of vomeronasal receptors [V1Rs and V2Rs (12,13,19,25,35,341)], 2) a family of aminergic receptors, the so-called TAARs (19,25,152,342,343), 3) FPRs (13,35,158,261,344), and 4) MS4As (19,38,149,150). The two families of vomeronasal receptors were named according to their expression site in mammals, the VNO.…”

Section: Receptor Gene Familiesmentioning

confidence: 99%

Principles of odor coding in vertebrates and artificial chemosensory systems

Manzini

Schild

Natale

2022

Physiological Reviews

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The biological olfactory system is the sensory system responsible for the detection of the chemical composition of the environment. Several attempts to mimic biological olfactory systems have led to various artificial olfactory systems using different technical approaches. Here we provide a parallel description of biological olfactory systems and their technical counterparts. We start with a presentation of the input to the systems, the stimuli, and treat the interface between the external world and the environment where receptor neurons or artificial chemosensors reside. We then delineate the functions of receptor neurons and chemosensors as well as their overall I-O relationships. Up to this point, our account of the systems goes along similar lines. The next processing steps differ considerably: while in biology the processing step following the receptor neurons is the "integration" and "processing" of receptor neuron outputs in the olfactory bulb, this step has various realizations in electronic noses. For a long period of time, the signal processing stages beyond the olfactory bulb, i.e., the higher olfactory centers were little studied. Only recently there has been a marked growth of studies tackling the information processing in these centers. In electronic noses, a third stage of processing has virtually never been considered. In this review, we provide an up-to-date overview of the current knowledge of both fields and, for the first time, attempt to tie them together. We hope it will be a breeding ground for better information, communication, and data exchange between very related but so far little connected fields.

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“…For instance, the human genome contains only six functional and single-copy trace amine–associated receptor genes ( 21 , 22 ). Humans also lack vomeronasal-specific formyl peptide receptors and vomeronasal type 2 receptors ( 21 , 22 , 23 ). Moreover, only five functional vomeronasal type 1 receptors have been reported to date; however, their direct functional importance in pheromone detection is highly debatable ( 24 ).…”

mentioning

confidence: 99%

OdoriFy: A conglomerate of artificial intelligence–driven prediction engines for olfactory decoding

Gupta

Mittal

Agrawal

et al. 2021

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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From immune to olfactory expression: neofunctionalization of formyl peptide receptors

Cited by 12 publications

References 42 publications

SARS-CoV-2 infects human GnRH neurons and tanycytes, disrupting hypothalamic-pituitary hormonal axes

SARS-CoV-2 infects human GnRH neurons and tanycytes, disrupting hypothalamic-pituitary hormonal axes

Principles of odor coding in vertebrates and artificial chemosensory systems

OdoriFy: A conglomerate of artificial intelligence–driven prediction engines for olfactory decoding

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