C-terminal phosphorylation of latrophilin-1/ADGRL1 affects the interaction between its fragments.
Ann N Y Acad Sci
; 1456(1): 122-143, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31553068
ABSTRACT
Latrophilin-1 is an adhesion G protein-coupled receptor that mediates the effect of α-latrotoxin, causing massive release of neurotransmitters from nerve terminals and endocrine cells. Autoproteolysis cleaves latrophilin-1 into two parts the extracellular N-terminal fragment (NTF) and the heptahelical C-terminal fragment (CTF). NTF and CTF can exist as independent proteins in the plasma membrane, but α-latrotoxin binding to NTF induces their association and G protein-mediated signaling. We demonstrate here that CTF in synapses is phosphorylated on multiple sites. Phosphorylated CTF has a high affinity for NTF and copurifies with it on affinity columns and sucrose density gradients. Dephosphorylated CTF has a lower affinity for NTF and can behave as a separate protein. α-Latrotoxin (and possibly other ligands of latrophilin-1) binds both to the NTF-CTF complex and receptor-like protein tyrosine phosphatase σ, bringing them together. This leads to CTF dephosphorylation and facilitates CTF release from the complex. We propose that ligand-dependent phosphorylation-dephosphorylation of latrophilin-1 could affect the interaction between its fragments and functions as a G protein-coupled receptor.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Peptídeos
/
Receptores Acoplados a Proteínas G
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Ann N Y Acad Sci
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Reino Unido