Satellite glial GPR37L1 and its ligand maresin 1 regulate potassium channel signaling and pain homeostasis
G protein-coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR with largely unknown functions. Here we report that Gpr37l1/GRP37L1 ranks among the most highly expressed GPCR transcripts in mouse and human dorsal root ganglia (DRGs), selectively expressed in satellite glial cells (SGCs). Peripheral neuropathy induced by streptozotoxin (STZ) and paclitaxel (PTX) led to reduced GPR37L1 expression on the plasma membrane expression in mouse and human DRGs. Transgenic mice with Gpr37l1 deficiency exhibited impaired resolution of neuropathic pain symptoms following PTX and STZ-induced pain, whereas overexpression of Gpr37l1 in mouse DRGs reversed pain. GPR37L1 is co-expressed with potassium channels, including KCNJ10 (Kir4.1) in mouse SGCs and both KCNJ3 (Kir3.1) and KCNJ10 in human SGCs. GPR37L1 regulates the surface expression and function of the potassium channels. Notably, the pro-resolving lipid mediator maresin 1 (MaR1) serves as a ligand of GPR37L1 and enhances KCNJ10 or KCNJ3-mediated potassium influx in SGCs through GPR37L1. Chemotherapy suppressed KCNJ10 expression and function in SGCs, which MaR1 rescued through GPR37L1. Finally, genetic analysis revealed that the GPR37L1-E296K variant increased chronic pain risk by destabilizing the protein and impairing the protein's function. Thus, GPR37L1 in SGCs offers a new therapeutic target for the protection of neuropathy and chronic pain.
| Errataetall: | |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
The Journal of clinical investigation - (2024) vom: 26. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Bang, Sangsu [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
G proteincoupled receptors |
|---|
| Anmerkungen: |
Date Revised 08.04.2024 published: Print-Electronic UpdateOf: bioRxiv. 2023 Dec 05;:. - PMID 38106084 Citation Status Publisher |
|---|
| doi: |
10.1172/JCI173537 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM370199200 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM370199200 | ||
| 003 | DE-627 | ||
| 005 | 20240408232841.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240327s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1172/JCI173537 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1369.xml |
| 035 | |a (DE-627)NLM370199200 | ||
| 035 | |a (NLM)38530364 | ||
| 035 | |a (PII)e173537 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Bang, Sangsu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Satellite glial GPR37L1 and its ligand maresin 1 regulate potassium channel signaling and pain homeostasis |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 08.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a UpdateOf: bioRxiv. 2023 Dec 05;:. - PMID 38106084 | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a G protein-coupled receptor 37-like 1 (GPR37L1) is an orphan GPCR with largely unknown functions. Here we report that Gpr37l1/GRP37L1 ranks among the most highly expressed GPCR transcripts in mouse and human dorsal root ganglia (DRGs), selectively expressed in satellite glial cells (SGCs). Peripheral neuropathy induced by streptozotoxin (STZ) and paclitaxel (PTX) led to reduced GPR37L1 expression on the plasma membrane expression in mouse and human DRGs. Transgenic mice with Gpr37l1 deficiency exhibited impaired resolution of neuropathic pain symptoms following PTX and STZ-induced pain, whereas overexpression of Gpr37l1 in mouse DRGs reversed pain. GPR37L1 is co-expressed with potassium channels, including KCNJ10 (Kir4.1) in mouse SGCs and both KCNJ3 (Kir3.1) and KCNJ10 in human SGCs. GPR37L1 regulates the surface expression and function of the potassium channels. Notably, the pro-resolving lipid mediator maresin 1 (MaR1) serves as a ligand of GPR37L1 and enhances KCNJ10 or KCNJ3-mediated potassium influx in SGCs through GPR37L1. Chemotherapy suppressed KCNJ10 expression and function in SGCs, which MaR1 rescued through GPR37L1. Finally, genetic analysis revealed that the GPR37L1-E296K variant increased chronic pain risk by destabilizing the protein and impairing the protein's function. Thus, GPR37L1 in SGCs offers a new therapeutic target for the protection of neuropathy and chronic pain | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a G proteincoupled receptors | |
| 650 | 4 | |a Homeostasis | |
| 650 | 4 | |a Neurological disorders | |
| 650 | 4 | |a Neuroscience | |
| 700 | 1 | |a Jiang, Changyu |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Chandra, Sharat |e verfasserin |4 aut | |
| 700 | 1 | |a McGinnis, Aidan |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a He, Qianru |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yize |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zilong |e verfasserin |4 aut | |
| 700 | 1 | |a Ao, Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Parisien, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Oliveira Fernandes de Araujo, Lorenna |e verfasserin |4 aut | |
| 700 | 1 | |a Jahangiri Esfahani, Sahel |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qin |e verfasserin |4 aut | |
| 700 | 1 | |a Tonello, Raquel |e verfasserin |4 aut | |
| 700 | 1 | |a Berta, Temugin |e verfasserin |4 aut | |
| 700 | 1 | |a Diatchenko, Luda |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Ru-Rong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of clinical investigation |d 1924 |g (2024) vom: 26. März |w (DE-627)NLM000005487 |x 1558-8238 |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:26 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1172/JCI173537 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 26 |c 03 | ||