Document Detail

Latrophilin 1 and its endogenous ligand Lasso/teneurin-2 form a high-affinity transsynaptic receptor pair with signaling capabilities.
MedLine Citation:
PMID:  21724987     Owner:  NLM     Status:  MEDLINE    
Latrophilin 1 (LPH1), a neuronal receptor of α-latrotoxin, is implicated in neurotransmitter release and control of presynaptic Ca(2+). As an "adhesion G-protein-coupled receptor," LPH1 can convert cell surface interactions into intracellular signaling. To examine the physiological functions of LPH1, we used LPH1's extracellular domain to purify its endogenous ligand. A single protein of ∼275 kDa was isolated from rat brain and termed Lasso. Peptide sequencing and molecular cloning have shown that Lasso is a splice variant of teneurin-2, a brain-specific orphan cell surface receptor with a function in neuronal pathfinding and synaptogenesis. We show that LPH1 and Lasso interact strongly and specifically. They are always copurified from rat brain extracts. Coculturing cells expressing LPH1 with cells expressing Lasso leads to their mutual attraction and formation of multiple junctions to which both proteins are recruited. Cells expressing LPH1 form chimerical synapses with hippocampal neurons in cocultures; LPH1 and postsynaptic neuronal protein PSD-95 accumulate on opposite sides of these structures. Immunoblotting and immunoelectron microscopy of purified synapses and immunostaining of cultured hippocampal neurons show that LPH1 and Lasso are enriched in synapses; in both systems, LPH1 is presynaptic, whereas Lasso is postsynaptic. A C-terminal fragment of Lasso interacts with LPH1 and induces Ca(2+) signals in presynaptic boutons of hippocampal neurons and in neuroblastoma cells expressing LPH1. Thus, LPH1 and Lasso can form transsynaptic complexes capable of inducing presynaptic Ca(2+) signals, which might affect synaptic functions.
John-Paul Silva; Vera G Lelianova; Yaroslav S Ermolyuk; Nickolai Vysokov; Paul G Hitchen; Otto Berninghausen; M Atiqur Rahman; Alice Zangrandi; Sara Fidalgo; Alexander G Tonevitsky; Anne Dell; Kirill E Volynski; Yuri A Ushkaryov
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-07-01
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-20     Completed Date:  2011-10-03     Revised Date:  2014-10-14    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12113-8     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
GENBANK/JF784339;  JF784340;  JF784341;  JF784342;  JF784343;  JF784344;  JF784345;  JF784346;  JF784347;  JF784348;  JF784349;  JF784350;  JF784351;  JF784352;  JF784353;  JF784354;  JF784355;  JF784356;  JF784357;  JF784358;  JF784359
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MeSH Terms
Base Sequence
Calcium Signaling / physiology*
Cloning, Molecular
Hippocampus / metabolism*,  physiology
Microscopy, Immunoelectron
Molecular Sequence Data
Nerve Tissue Proteins / genetics*,  metabolism*
Receptors, Cell Surface / genetics*,  metabolism*
Receptors, Peptide / metabolism*
Sequence Analysis, DNA
Synapses / metabolism*
Synaptic Transmission / physiology*
Grant Support
BB/D523078/1//Biotechnology and Biological Sciences Research Council; BBC5196701//Biotechnology and Biological Sciences Research Council; BBF0083091//Biotechnology and Biological Sciences Research Council; G0600089//Medical Research Council; WT083199MF//Wellcome Trust
Reg. No./Substance:
0/Nerve Tissue Proteins; 0/Odz2 protein, rat; 0/Receptors, Cell Surface; 0/Receptors, Peptide; 0/alpha-latrotoxin receptor

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