The very large G-protein-coupled receptor 1 (VLGR1/ADGRV1) is the largest member
of the adhesion G-protein-coupled receptor (ADGR) family. Mutations in VLGR1/ADGRV1 cause
human Usher syndrome (USH), a form of hereditary deaf-blindness, and have been additionally
linked to epilepsy. In the absence of tangible knowledge of the molecular function and signaling
of VLGR1, the pathomechanisms underlying the development of these diseases are still unknown.
Our study aimed to identify novel, previously unknown protein networks associated with VLGR1
in order to describe new functional cellular modules of this receptor. Using affinity proteomics, we
have identified numerous new potential binding partners and ligands of VLGR1. Tandem affinity
purification hits were functionally grouped based on their Gene Ontology terms and associated with
functional cellular modules indicative of functions of VLGR1 in transcriptional regulation, splicing,
cell cycle regulation, ciliogenesis, cell adhesion, neuronal development, and retinal maintenance. In
addition, we validated the identified protein interactions and pathways in vitro and in situ. Our
data provided new insights into possible functions of VLGR1, related to the development of USH
and epilepsy, and also suggest a possible role in the development of other neuronal diseases such as
Alzheimer’s disease.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:87161 |
| Date | 22 September 2023 |
| Creators | Knapp, Barbara, Roedig, Jens, Roedig, Heiko, Krzysko, Jacek, Horn, Nicola, Güler, Baran E., Kusuluri, Deva Krupakar, Yildirim, Adem, Boldt, Karsten, Ueffing, Marius, Liebscher, Ines, Wolfrum, Uwe |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 3108, 10.3390/molecules27103108 |
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