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C-terminal phosphorylation of latrophilin-1/ADGRL1 affects the interaction between its fragments

Rahman, M. Atiqur, Manser, Catherine, Benlaouer, Ouafa, Suckling, Jason, Blackburn, Jennifer K., Silva, John, Ushkaryov, Yuri A. (2019) C-terminal phosphorylation of latrophilin-1/ADGRL1 affects the interaction between its fragments. The Annals of the New York Academy of Sciences, 1456 (1). pp. 122-143. ISSN 1749-6632. (doi:10.1111/nyas.14242) (KAR id:76429)

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Latrophilin-1 is an Adhesion G protein-coupled receptor, which 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 co-purifies with it on affinity columns and on 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 to 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 phosphorylationdephosphorylation of latrophilin-1 could affect the interaction between its fragments and its functions as a G protein-coupled receptor.

Item Type: Article
DOI/Identification number: 10.1111/nyas.14242
Uncontrolled keywords: latrophilin, adhesion GPCRs, fragment, phosphorylation, α-latrotoxin
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Yuri Ushkarev
Date Deposited: 12 Sep 2019 10:52 UTC
Last Modified: 16 Feb 2021 14:07 UTC
Resource URI: (The current URI for this page, for reference purposes)
Ushkaryov, Yuri A.:
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