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C‐terminal phosphorylation of latrophilin‐1/ADGRL1 affects the interaction between its fragments
Author(s) -
Rahman M. Atiqur,
Manser Catherine,
Benlaouer Ouafa,
Suckling Jason,
Blackburn Jennifer K.,
Silva JohnPaul,
Ushkaryov Yuri A.
Publication year - 2019
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.14242
Subject(s) - dephosphorylation , phosphorylation , chemistry , microbiology and biotechnology , receptor , biophysics , biochemistry , tyrosine , protein tyrosine phosphatase , phosphatase , biology
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.