# Mechanosensitive adhesion G protein-coupled receptors: Insights from health and disease

**Authors:** Shiying Sun, Wen Wang

PMC · DOI: 10.1016/j.gendis.2024.101267 · Genes & Diseases · 2024-03-16

## TL;DR

This paper reviews how adhesion G protein-coupled receptors sense mechanical forces and their roles in health and disease.

## Contribution

It provides a comprehensive overview of the structure, activation, and disease-related functions of mechanosensitive aGPCRs.

## Key findings

- aGPCRs have unique structures that enable them to sense mechanical stimuli.
- Mechanosensitive aGPCRs are linked to various lesion manifestations in diseases.
- Their activation mechanisms are crucial for intracellular signal transduction.

## Abstract

Ontogeny cannot be separated from mechanical forces. Cells are continuously subjected to different types of mechanical stimuli that convert into intracellular signals through mechanotransduction. As a member of the G protein-coupled receptor superfamily, adhesion G protein-coupled receptors (aGPCRs) have attracted extensive attention due to their unique extracellular domain and adhesion properties. In the past few decades, increasing evidence has indicated that sensing mechanical stimuli may be one of the main physiological activities of aGPCRs. Here, we review the general structure and activation mechanisms of these receptors and highlight the lesion manifestations relevant to each mechanosensitive aGPCR.

## Full-text entities

- **Genes:** Adgrg5 (adhesion G protein-coupled receptor G5) [NCBI Gene 382045] {aka Gm1109, Gpr114, PGR27}, DLG4 (discs large MAGUK scaffold protein 4) [NCBI Gene 1742] {aka MRD62, PSD95, SAP-90, SAP90}, CD9 (CD9 molecule) [NCBI Gene 928] {aka BTCC-1, DRAP-27, MIC3, MRP-1, TSPAN-29, TSPAN29}, TENM2 (teneurin transmembrane protein 2) [NCBI Gene 57451] {aka ODZ2, TEN-M2, TEN2, TNM2, ten-2}, TGM2 (transglutaminase 2) [NCBI Gene 7052] {aka G(h), TG(C), TGC, hTG2, tTG}, PRKD1 (protein kinase D1) [NCBI Gene 5587] {aka CHDED, PKC-MU, PKCM, PKD, PKD1, PRKCM}, ADGRL3 (adhesion G protein-coupled receptor L3) [NCBI Gene 23284] {aka CIRL3, CL3, LEC3, LPHN3}, AGRN (agrin) [NCBI Gene 375790] {aka AGRIN, CMS8, CMSPPD}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, ADGRF2P (adhesion G protein-coupled receptor F2, pseudogene) [NCBI Gene 222611] {aka ADGRF2, GPR111, PGR20, hGPCR35}, GRK6 (G protein-coupled receptor kinase 6) [NCBI Gene 2870] {aka GPRK6}, ADGRE2 (adhesion G protein-coupled receptor E2) [NCBI Gene 30817] {aka CD312, CD97, EMR2, VBU}, DLG1 (discs large MAGUK scaffold protein 1) [NCBI Gene 1739] {aka DLGH1, SAP-97, SAP97, hdlg}, GALNS (galactosamine (N-acetyl)-6-sulfatase) [NCBI Gene 2588] {aka GALNAC6S, GAS, GalN6S, MPS4A}, PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, GNA15 (G protein subunit alpha 15) [NCBI Gene 2769] {aka GNA16, HG1L}, ADGRV1 (adhesion G protein-coupled receptor V1) [NCBI Gene 84059] {aka FEB4, GPR98, MASS1, USH2B, USH2C, VLGR1}, SCT (secretin) [NCBI Gene 6343], Adgrf5 (adhesion G protein-coupled receptor F5) [NCBI Gene 224792] {aka 8430401C09Rik, 9330185D23, Gpr116, mKIAA0758}, Adgrg6 (adhesion G protein-coupled receptor G6) [NCBI Gene 215798] {aka 1190004A11Rik, DREG, Gm222, Gpr126}, ADGRG5 (adhesion G protein-coupled receptor G5) [NCBI Gene 221188] {aka GPR114, PGR27}, ADGRG6 (adhesion G protein-coupled receptor G6) [NCBI Gene 57211] {aka APG1, DREG, GPR126, LCCS9, PR126, PS1TP2}, Adgrg1 (adhesion G protein-coupled receptor G1) [NCBI Gene 14766] {aka Cyt28, Gpr56, TM7LN4, TM7XN1}, ARRB1 (arrestin beta 1) [NCBI Gene 408] {aka ARB1, ARR1}, Adgre5 (adhesion G protein-coupled receptor E5) [NCBI Gene 26364] {aka Cd97, TM7LN1}, nompC (no mechanoreceptor potential C) [NCBI Gene 33768] {aka CG11020, CG17468, CT30855, DmNompC, Dmel\CG11020, ORE-13}, Cirl (Calcium-independent receptor for alpha-latrotoxin) [NCBI Gene 35846] {aka ADGRL3, BcDNA:GH07331, CG8639, Dmel\CG8639, anon-WO0170980.7, anon-WO0170980.8}, Egf (epidermal growth factor) [NCBI Gene 13645], SHBG (sex hormone binding globulin) [NCBI Gene 6462] {aka ABP, SBP, TEBG}, FNDC4 (fibronectin type III domain containing 4) [NCBI Gene 64838] {aka FRCP1}, CFHR1 (complement factor H related 1) [NCBI Gene 3078] {aka CFHL, CFHL1, CFHL1P, CFHR1P, FHL-1, FHR-1}, ADGRF4 (adhesion G protein-coupled receptor F4) [NCBI Gene 221393] {aka GPR115, PGR18}, PRNP (prion protein (Kanno blood group)) [NCBI Gene 5621] {aka ASCR, AltPrP, CD230, CJD, GSS, KURU}, ADGRL1 (adhesion G protein-coupled receptor L1) [NCBI Gene 22859] {aka CIRL1, CL1, DEDBANP, LEC2, LPHN1}, CD55 (CD55 molecule (Cromer blood group)) [NCBI Gene 1604] {aka CHAPLE, CR, CROM, DAF, TC}, TJP1 (tight junction protein 1) [NCBI Gene 7082] {aka ZO-1}, SUCLG1 (succinate-CoA ligase GDP/ADP-forming subunit alpha) [NCBI Gene 8802] {aka GALPHA, MTDPS9, SUCLA1}, GPR166P (G protein-coupled receptor 166, pseudogene) [NCBI Gene 442206] {aka GPCR, PGR9}, NFIC (nuclear factor I C) [NCBI Gene 4782] {aka CTF, CTF5, NF-I, NF-I/C, NF1-C, NFI}, SFTPD (surfactant protein D) [NCBI Gene 6441] {aka COLEC7, PSP-D, SFTP4, SP-D}, SEA (S13 erythroblastosis (avian) oncogene homolog) [NCBI Gene 6395], Glul (glutamate-ammonia ligase) [NCBI Gene 14645] {aka GS, Glns}, Gna13 (guanine nucleotide binding protein, alpha 13) [NCBI Gene 14674] {aka Galpha13}, Sftpd (surfactant associated protein D) [NCBI Gene 20390] {aka PSP-D, SP-D, Sfpd, Sftp4}, ADGRG1 (adhesion G protein-coupled receptor G1) [NCBI Gene 9289] {aka BFPP, BPPR, CDCBM14B, CDCBM15A, GPR56, TM7LN4}, RHO (rhodopsin) [NCBI Gene 6010] {aka CSNBAD1, OPN2, RP4}, RASGRF1 (Ras protein specific guanine nucleotide releasing factor 1) [NCBI Gene 5923] {aka CDC25, CDC25L, GNRP, GRF1, GRF55, H-GRF55}, ADGRA1 (adhesion G protein-coupled receptor A1) [NCBI Gene 84435] {aka GPR123}, ARHGEF25 (Rho guanine nucleotide exchange factor 25) [NCBI Gene 115557] {aka GEFT, p63RhoGEF}, ADGRF5 (adhesion G protein-coupled receptor F5) [NCBI Gene 221395] {aka GPR116, KPG_001}, BMP1 (bone morphogenetic protein 1) [NCBI Gene 649] {aka OI13, PCOLC, PCP, TLD}, adgrg6 (adhesion G protein-coupled receptor G6) [NCBI Gene 561970] {aka gpr126, si:ch211-202p1.3}, ARHGEF2 (Rho/Rac guanine nucleotide exchange factor 2) [NCBI Gene 9181] {aka GEF, GEF-H1, GEFH1, LFP40, Lfc, NEDMHM}, nan (nanchung) [NCBI Gene 39571] {aka CG5842, CT18317, DmNan, Dmel\CG5842, Iav, OCR}, GNAI1 (G protein subunit alpha i1) [NCBI Gene 2770] {aka Gi, HG1B, NEDHISB}, Adgrv1 (adhesion G protein-coupled receptor V1) [NCBI Gene 110789] {aka Frings, Gpr98, Mass1, Mgr1, VLGR1}, ADGRE5 (adhesion G protein-coupled receptor E5) [NCBI Gene 976] {aka CD97, TM7LN1}, CNTN6 (contactin 6) [NCBI Gene 27255] {aka NB3}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, C1S (complement C1s) [NCBI Gene 716] {aka EDSPD2}
- **Diseases:** acute myeloid leukemia (MESH:D015470), cancer (MESH:D009369), Leber's hereditary optic neuropathy (MESH:D029242), aggressive periodontitis (MESH:D010520), hepatocellular carcinoma (MESH:D006528), immune diseases (MESH:D007154), musculoskeletal disorders (MESH:D009140), metastasis (MESH:D009362), NTF (MESH:D012892), melanoma (MESH:D008545), depression (MESH:D003866), myocardial infarction (MESH:D009203), colorectal cancer (MESH:D015179), inflammation (MESH:D007249), pain (MESH:D010146), frontoparietal (MESH:C536673), rhabdomyosarcoma (MESH:D012208), Alzheimer's disease (MESH:D000544), arthritis (MESH:D001168), BFPP (MESH:C564652), glioblastoma (MESH:D005909), breast cancer (MESH:D001943), diabetes (MESH:D003920), leukemic (MESH:D007938), adolescent idiopathic scoliosis (OMIM:181800), retinitis pigmentosa (MESH:D012174), hyperglycemia (MESH:D006943), hypertrophy (MESH:D006984), osteosarcoma (MESH:D012516), neurological diseases (MESH:D020271), platelet plug (MESH:D001791), periodontitis (MESH:D010518), cognitive and language delay (MESH:D007805), microcephaly (MESH:D008831), bleeding (MESH:D006470), arthrogryposis multiplex congenita (MESH:D001176), epilepsy (MESH:D004827), neurological disorders (MESH:D009461), urticaria (MESH:D014581), vibratory urticaria (MESH:C536612), thyroid cancer (MESH:D013964), brain malformation (MESH:D020785), sensorineural hearing loss (MESH:D006319), auditory impairment (MESH:D006311), polymicrogyria (MESH:D065706), autism spectrum disorder (MESH:D000067877), prostate cancer (MESH:D011471), substance use disorder (MESH:D019966), Usher syndrome type 2C (MESH:C536492), muscle hypertrophy (MESH:C536106), attention deficit and hyperactivity disorder (MESH:D001289), chronic kidney disease (MESH:D051436), thrombus occlusion (MESH:D013927), rheumatoid arthritis (MESH:D001172), pectus excavatum (MESH:D005660), schizophrenia (MESH:D012559), psoriasis (MESH:D011565), osteoporosis (MESH:D010024), multiple sclerosis (MESH:D009103), vascular injury (MESH:D057772)
- **Chemicals:** rhamnose (MESH:D012210), dihydromunduletone (MESH:C000618267), phosphatidylserine (MESH:D010718), DS (MESH:D003871), glucose (MESH:D005947), progesterone (MESH:D011374), GDP (MESH:D006153), calcium (MESH:D002118), GTP (MESH:D006160), lipid (MESH:D008055), 7TM (-), 3-alpha-acetoxydihydrodeo-xygedunin (MESH:C000708852)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Drosophila melanogaster (fruit fly, species) [taxon 7227], Danio rerio (leopard danio, species) [taxon 7955]
- **Mutations:** p. C492Y, rs6551665, rs6570507, L640R, rs536714306

## Full text

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## References

155 references — full list in the complete paper: https://tomesphere.com/paper/PMC11810715/full.md

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Source: https://tomesphere.com/paper/PMC11810715