Olfactory marker protein elevates basal cAMP concentration

Nakashima, Noriyuki; Nakashima, Kie; Nakashima, Akiko; Takano, Makoto

doi:10.1016/j.bbrc.2020.07.087

Cited by 10 publications

(5 citation statements)

References 35 publications

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“…OMP has been suspected for a long time to play a very important role in OSN maturation and OSN plasticity notably induced by external stimuli (Lee et al 2011;Kass et al 2013a). Astonishingly, a very recent study demonstrated that OMP was a cAMP buffer which was completely unexpected (Nakashima et al 2020). Similarly, future studies may reveal previously unknown roles for OSN response modulators.…”

Section: Discussionmentioning

confidence: 88%

Modulation of olfactory signal detection in the olfactory epithelium: focus on the internal and external environment, and the emerging role of the immune system

2021

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Detection and discrimination of odorants by the olfactory system plays a pivotal role in animal survival. Olfactory-based behaviors must be adapted to an ever-changing environment. Part of these adaptations includes changes of odorant detection by olfactory sensory neurons localized in the olfactory epithelium. It is now well established that internal signals such as hormones, neurotransmitters, or paracrine signals directly affect the electric activity of olfactory neurons. Furthermore, recent data have shown that activity-dependent survival of olfactory neurons is important in the olfactory epithelium. Finally, as olfactory neurons are directly exposed to environmental toxicants and pathogens, the olfactory epithelium also interacts closely with the immune system leading to neuroimmune modulations. Here, we review how detection of odorants can be modulated in the vertebrate olfactory epithelium. We choose to focus on three cellular types of the olfactory epithelium (the olfactory sensory neuron, the sustentacular and microvillar cells) to present the diversity of modulation of the detection of odorant in the olfactory epithelium. We also present some of the growing literature on the importance of immune cells in the functioning of the olfactory epithelium, although their impact on odorant detection is only just beginning to be unravelled.

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Section: Discussionmentioning

confidence: 88%

Modulation of olfactory signal detection in the olfactory epithelium: focus on the internal and external environment, and the emerging role of the immune system

2021

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“…These phenomena have been demonstrated to be caused by the increased overall basal activity due to the prolonged response of cAMP in Omp −/− mice in response to odorants 17 . Recent studies have reported that OMP directly binds cAMP to regulate the level of freely available cAMP and to control the basal cAMP pool 34 – 36 . Thus, by buffering the cAMP levels, OMP prevents persistent depolarization of OR neurons, enabling a sustained response to repeated stimuli.…”

Section: Discussionmentioning

confidence: 99%

Olfactory marker protein regulation of glucagon secretion in hyperglycemia

Han

Bao

et al. 2022

Exp Mol Med

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The olfactory marker protein (OMP), which is also expressed in nonolfactory tissues, plays a role in regulating the kinetics and termination of olfactory transduction. Thus, we hypothesized that OMP may play a similar role in modulating the secretion of hormones involved in Ca2+ and cAMP signaling, such as glucagon. In the present study, we confirmed nonolfactory α-cell-specific OMP expression in human and mouse pancreatic islets as well as in the murine α-cell line αTC1.9. Glucagon and OMP expression increased under hyperglycemic conditions. Omp knockdown in hyperglycemic αTC1.9 cells using small-interfering RNA (siRNA) reduced the responses to glucagon release and the related signaling pathways compared with the si-negative control. The OMPlox/lox;GCGcre/w mice expressed basal glucagon levels similar to those in the wild-type OMPlox/lox mice but showed resistance against streptozotocin-induced hyperglycemia. The ectopic olfactory signaling events in pancreatic α-cells suggest that olfactory receptor pathways could be therapeutic targets for reducing excessive glucagon levels.

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“…Reporter gene expression protocol as previously described with a few modifications (Melnikov et al, 2014; Nakashima et al, 2020; Noack et al, 2022). Neuro2a cells were cultured at a density of 2.0 ×10 5 /well in 6-well plates transiently transfected with 1µg of plasmid/well, which included 500 ng of CREs-min.…”

Section: Methodsmentioning

confidence: 99%

Regulatory Mechanisms Orchestrating Cellular Diversity in Cd36+ Olfactory Sensory Neurons Revealed by Single-Cell Multi-omics Analysis

Yang,

Shi,

et al. 2023

Preprint

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The olfactory system relies on the precise expression of olfactory receptor (OR) genes in individual olfactory sensory neurons (OSNs) to detect and discriminate a vast array of odorants. Recent discoveries have revealed remarkable complexity and diversity within OSNs, including the existence of two distinct OSN populations based on high-affinity receptor Cd36 expression. However, the regulatory mechanisms governing this cellular diversity in the same cell type remain elusive. To address these questions, we conducted single-cell multi-omics analyses of mature OSNs in the mouse olfactory epithelium. Firstly, we systematically revealed the transcriptome diversity and spatial distribution of Cd36+ OSNs and found a specific subset of olfactory receptors co-expressed with Cd36 in a deterministic manner. scATAC-seq profiling of chromatin landscape demonstrated a divergence between Cd36+ OSNs and Cd36- OSNs, including differential accessibility of cis-elements. By integrating transcriptome and epigenome profiling of OSN lineage-associated cell types, we revealed that the processes governing this diversity are initiated at the immature OSNs stage, where cellular diversity was first set by the lineage-specific binding of Lhx2 at Hdac9 enhancer. Hdac9, which is specifically expressed in the Cd36- OSN lineage, functions as a histone deacetylase and may repress the transcription of Mef2-dependent genes that contribute to Cd36+ OSN diversity. By gene regulation network analysis, we revealed Mef2a and Tshz1 as the key transcription factors, orchestrating the transcriptome diversity of Cd36+ OSNs. Remarkably, we identified and confirmed Tshz1 as a critical transcription factor that directly promotes Cd36 expression in OSNs through enhancer binding. Our study unravels the intricate regulatory landscape and principles governing cellular diversity in the olfactory system. These findings provide valuable insights into the regulation principles underlying neuronal heterogeneity and its functional implications.

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Olfactory marker protein elevates basal cAMP concentration

Cited by 10 publications

References 35 publications

Modulation of olfactory signal detection in the olfactory epithelium: focus on the internal and external environment, and the emerging role of the immune system

Modulation of olfactory signal detection in the olfactory epithelium: focus on the internal and external environment, and the emerging role of the immune system

Olfactory marker protein regulation of glucagon secretion in hyperglycemia

Regulatory Mechanisms Orchestrating Cellular Diversity in Cd36+ Olfactory Sensory Neurons Revealed by Single-Cell Multi-omics Analysis

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