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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 28, 2024 |
| Title |
Role of iRhom2 in Olfaction: Implications for Odorant Receptor Regulation and Activity-dependent Adaptation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The cell surface metalloprotease ADAM17 and its binding partners iRhom2 and iRhom1 modulate cell-cell interactions by mediating the release of membrane proteins such as TNFa and EGFR-ligands from the cell surface. Most cell types express both iRhoms, though myeloid cells exclusively express iRhom2, and iRhom1 is the main iRhom in the mouse brain. Here we report that iRhom2 is uniquely expressed in olfactory sensory neurons (OSNs), highly specialized cells expressing one olfactory receptor (OR) from a repertoire of over a thousand OR genes in mice. iRhom2-/- mice had no evident morphological defects in the olfactory epithelium (OE), yet RNAseq analysis revealed differential expression of a small subset of ORs. Notably, while the majority of ORs remain unaffected in iRhom2-/- OE, OSNs expressing ORs that are enriched in iRhom2-/- OE showed fewer gene expression changes upon odor environmental changes than the majority of OSNs. Moreover, we discovered an inverse correlation between the expression of iRhom2 compared to OSN activity genes and that odor exposure negatively regulates iRhom2 expression. Given that ORs are specialized G-protein coupled receptors (GPCRs) and many GPCRs activate iRhom2/ADAM17, we investigated if ORs could activate iRhom2/ADAM17. Activation of OR2AT4 by its agonist sandalore in keratinocytes, where this receptor is ectopically expressed, leads to ERK1/2 phosphorylation, likely via an iRhom2/ADAM17-dependent pathway. Taken together, these findings point to a mechanism by which odor stimulation of OSNs activates iRhom2/ADAM17 catalytic activity, resulting in downstream transcriptional changes to the OR repertoire and activity genes, and driving a negative feedback loop to downregulate iRhom2 expression.
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| Overall design |
To investigate gene expression differences between iRhom2-/- and WT olfactory epithelium, main olfactory epitheliums were harvested at various ages and bulk sequenced.
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/38892263/
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| Contributor(s) |
Azzopardi SA, Lu H, Monette S, Rabinowitsch AI, Salmon JE, Matsunami H, Blobel CP |
| Citation(s) |
38892263 |
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| Submission date |
May 22, 2024 |
| Last update date |
Sep 01, 2024 |
| Contact name |
Carl Blobel |
| E-mail(s) |
blobelc@hss.edu
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| Organization name |
Hospital for Special Surgery, Research Institute
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| Street address |
515 East 71st street
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| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10021 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (24)
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| GSM8287166 |
MOE, iRhom2-/-, 10 wks, rep1 |
| GSM8287167 |
MOE, iRhom2-/-, 10 wks, rep2 |
| GSM8287168 |
MOE, iRhom2-/-, 10 wks, rep3 |
| GSM8287169 |
MOE, WT, 8wks, rep1 |
| GSM8287170 |
MOE, WT, 8wks, rep2 |
| GSM8287171 |
MOE, WT, 8wks, rep3 |
| GSM8287172 |
MOE, iRhom2-/-, 8 wks, rep1 |
| GSM8287173 |
MOE, iRhom2-/-, 8 wks, rep2 |
| GSM8287174 |
MOE, iRhom2-/-, 8 wks, rep3 |
| GSM8287175 |
MOE, WT, 5wks, rep1 |
| GSM8287176 |
MOE, WT, 5wks, rep2 |
| GSM8287177 |
MOE, WT, 5wks, rep3 |
| GSM8287178 |
MOE, WT, 30wks, rep1 |
| GSM8287179 |
MOE, WT, 30wks, rep2 |
| GSM8287180 |
MOE, WT, 30wks, rep3 |
| GSM8287181 |
MOE, iRhom2-/-, 5wks, rep1 |
| GSM8287182 |
MOE, iRhom2-/-, 5wks, rep2 |
| GSM8287183 |
MOE, iRhom2-/-, 5wks, rep3 |
| GSM8287184 |
MOE, iRhom2-/-, 30wks, rep1 |
| GSM8287185 |
MOE, iRhom2-/-, 30wks, rep2 |
| GSM8287186 |
MOE, iRhom2-/-, 30wks, rep3 |
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| Relations |
| BioProject |
PRJNA1114810 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE268171_DE_allgene_WTvsKO_ALL.csv.gz |
3.0 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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