Affinity proteomics identifies novel functional modules related to adhesion GPCRs.
Ann N Y Acad Sci
; 1456(1): 144-167, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31441075
ABSTRACT
Adhesion G protein-coupled receptors (ADGRs) have recently become a target of intense research. Their unique protein structure, which consists of a G protein-coupled receptor combined with long adhesive extracellular domains, suggests a dual role in cell signaling and adhesion. Despite considerable progress in the understanding of ADGR signaling over the past years, the knowledge about ADGR protein networks is still limited. For most receptors, only a few interaction partners are known thus far. We aimed to identify novel ADGR-interacting partners to shed light on cellular protein networks that rely on ADGR function. For this, we applied affinity proteomics, utilizing tandem affinity purifications combined with mass spectrometry. Analysis of the acquired proteomics data provides evidence that ADGRs not only have functional roles at synapses but also at intracellular membranes, namely at the endoplasmic reticulum, the Golgi apparatus, mitochondria, and mitochondria-associated membranes (MAMs). Specifically, we found an association of ADGRs with several scaffold proteins of the membrane-associated guanylate kinases family, elementary units of the γ-secretase complex, the outer/inner mitochondrial membrane, MAMs, and regulators of the Wnt signaling pathways. Furthermore, the nuclear localization of ADGR domains together with their physical interaction with nuclear proteins and several transcription factors suggests a role of ADGRs in gene regulation.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteômica
/
Receptores Acoplados a Proteínas G
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article