Cells, co-auth.:W.Wahli

The Opioid Receptor Influences Circadian Rhythms in Human Keratinocytes through the β-Arrestin Pathway

Paul Bigliardi 1 2Seetanshu Junnarkar 3Chinmay Markale 1 2Sydney Lo 1 2Elena Bigliardi 1 2Alex Kalyuzhny 4Sheena Ong 3Ray Dunn 3 5Walter Wahli 5 6 7Mei Bigliardi-Qi 1 2

. 2024 Jan 25;13(3):232.

 doi: 10.3390/cells13030232.

Abstract

The recent emphasis on circadian rhythmicity in critical skin cell functions related to homeostasis, regeneration and aging has shed light on the importance of the PER2 circadian clock gene as a vital antitumor gene. Furthermore, delta-opioid receptors (DOPrs) have been identified as playing a crucial role in skin differentiation, proliferation and migration, which are not only essential for wound healing but also contribute to cancer development. In this study, we propose a significant association between cutaneous opioid receptor (OPr) activity and circadian rhythmicity. To investigate this link, we conducted a 48 h circadian rhythm experiment, during which RNA samples were collected every 5 h. We discovered that the activation of DOPr by its endogenous agonist Met-Enkephalin in N/TERT-1 keratinocytes, synchronized by dexamethasone, resulted in a statistically significant 5.6 h delay in the expression of the core clock gene PER2. Confocal microscopy further confirmed the simultaneous nuclear localization of the DOPr-β-arrestin-1 complex. Additionally, DOPr activation not only enhanced but also induced a phase shift in the rhythmic binding of β-arrestin-1 to the PER2 promoter. Furthermore, we observed that β-arrestin-1 regulates the transcription of its target genes, including PER2, by facilitating histone-4 acetylation. Through the ChIP assay, we determined that Met-Enkephalin enhances β-arrestin-1 binding to acetylated H4 in the PER2 promoter. In summary, our findings suggest that DOPr activation leads to a phase shift in PER2 expression via β-arrestin-1-facilitated chromatin remodeling. Consequently, these results indicate that DOPr, much like its role in wound healing, may also play a part in cancer development by influencing PER2.

Front Mol Biosci, Auth.: AM Cattaneo, group Benton

Heterologous investigation of metabotropic and ionotropic odorant receptors in ab3A neurons of Drosophila melanogaster

Johan Henning Pettersson 1Alberto Maria Cattaneo 1 2 3

. 2024 Jan 25:10:1275901.

 doi: 10.3389/fmolb.2023.1275901. eCollection 2023.

Abstract

In insects, antennal ionotropic receptors (IRs) and odorant receptors (ORs) are among the main sensors of olfactory cues. To functionally characterize the subunits from these receptors, the use of ab3A neurons from transgenic Drosophila melanogaster represented one of the most powerful tools, allowing the identification of ligands (deorphanization) and decrypting their pharmacological properties. However, further investigation is needed to shed light on possible metabotropic functionalities behind insect olfactory receptors and test potentials from the up-to-now-used empty neuronal systems to express subunits belonging to variegate receptor classes. In this project, we adopted the most updated system of Drosophila ab3A empty neurons to test various olfactory receptors, ranging from human ORs working as metabotropic G-protein coupled receptors to insect ionotropic IRs and ORs. Testing transgenic Drosophila expressing human ORs into ab3A neurons by single sensillum recording did not result in an OR response to ligands, but it rather re-established neuronal spiking from the empty neurons. When transgenic D. melanogaster expressed ionotropic IRs and ORs, both heterologous and cis-expressed IRs were non-functional, but the Drosophila suzukii OR19A1 subunit responded to a wide asset of ligands, distinguishing phasic or tonic compound-dependent effects. Despite the use of Drosophila ab3A neurons to test the activation of some metabotropic and ionotropic receptor subunits resulted non-functional, this study deorphanized a key OR of D. suzukii demonstrating its binding to alcohols, ketones, terpenes, and esters.

New Phytol, auth.: M.Legris

Light and temperature regulation of leaf morphogenesis in Arabidopsis

. 2023 Dec;240(6):2191-2196.

 doi: 10.1111/nph.19258. Epub 2023 Sep 15.

  • PMID: 37715490
  • DOI: 10.1111/nph.19258
  • Abstract
  • Leaves are the main photosynthetic organs in plants, and their anatomy is optimized for light interception and gas exchange. Although each species has a characteristic leaf anatomy, which depends on the genotype, leaves also show a large degree of developmental plasticity. Light and temperature regulate leaf development from primordia differentiation to late stages of blade expansion. While the molecular mechanisms of light and temperature signaling have been mostly studied in seedlings, in the latest years, research has focused on leaf development. Here, I will describe the latest work carried out in the environmental regulation of Arabidopsis leaf development, comparing signaling mechanisms between leaves and seedlings, highlighting the new discoveries, and pointing out the most exciting open questions.

Thu Feb 22 – Fri Feb 23, 2024 – Lausanne Omics Days 2024

This year, the scope of the Lausanne Genomics Days has broadened since it becomes the Lausanne Omics Days. It is still a 2-days international conference meant to share advances in genomics and their impact on biological research, applied to a wide range of topics(it does involve 5 UNIL departments CIGDBCDBMVDEE, and DMF).

It will take at UNIL / Genopode on February Thursday 22nd and Friday 23rd.

The conference offers 4 sessions:

  • Deep learning in Biology and Medicine (Chair: Prof. Sven Bergmann)
  • Variation in genome structure and organization (Chair: Prof. Sebastian Soyk)
  • Metabolomics – Towards understanding biological interaction (Chair: Prof. Philipp Engel)
  • Single cell and spatial transcriptomics (Chair: Prof. Tanja Schwander)

For detailed program and more information, please visit the event webpage

Registration is FREE of charge. Still, it is mandatory for organization purpose, in particular ensuring that there will not be food wasted (coffee breaks, lunch and apero are offered).

HERE is the direct link for registration

Attendance is worth 0.5 ECTS

Best regards

Julien Marquis, on behalf of the L0D2024 organization team
Head of Lausanne Genomics Technologies Facility (GTF)

Proc Natl Acad Sci U S A, auth.: group Franken

Cortical miR-709 links glutamatergic signaling to NREM sleep EEG slow waves in an activity-dependent manner

Konstantinos Kompotis # 1 2Géraldine M Mang # 1Jeffrey Hubbard 1Sonia Jimenez 1Yann Emmenegger 1Christos Polysopoulos 3Charlotte N Hor 1Leonore Wigger 4Sébastien S Hébert 5 6Valérie Mongrain 7 8 9Paul Franken 1

. 2024 Jan 16;121(3):e2220532121.

 doi: 10.1073/pnas.2220532121. Epub 2024 Jan 11.

Free article

Abstract

MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression that have been implicated in a plethora of neuronal processes. Nevertheless, their role in regulating brain activity in the context of sleep has so far received little attention. To test their involvement, we deleted mature miRNAs in post-mitotic neurons at two developmental ages, i.e., in early adulthood using conditional Dicer knockout (cKO) mice and in adult mice using an inducible conditional Dicer cKO (icKO) line. In both models, electroencephalographic (EEG) activity was affected and the response to sleep deprivation (SD) altered; while the rapid-eye-movement sleep (REMS) rebound was compromised in both, the increase in EEG delta (1 to 4 Hz) power during non-REMS (NREMS) was smaller in cKO mice and larger in icKO mice compared to controls. We subsequently investigated the effects of SD on the forebrain miRNA transcriptome and found that the expression of 48 miRNAs was affected, and in particular that of the activity-dependent miR-709. In vivo inhibition of miR-709 in the brain increased EEG power during NREMS in the slow-delta (0.75 to 1.75 Hz) range, particularly after periods of prolonged wakefulness. Transcriptome analysis of primary cortical neurons in vitro revealed that miR-709 regulates genes involved in glutamatergic neurotransmission. A subset of these genes was also affected in the cortices of sleep-deprived, miR-709-inhibited mice. Our data implicate miRNAs in the regulation of EEG activity and indicate that miR-709 links neuronal activity during wakefulness to brain synchrony during sleep through the regulation of glutamatergic signaling.