Latrophilin 1 and its endogenous ligand Lasso/teneurin-2 form a high-affinity transsynaptic receptor pair with signaling capabilities.

Authors: Silva, JP  Lelianova, VG  Ermolyuk, YS  Vysokov, N  Hitchen, PG  Berninghausen, O  Rahman, MA  Zangrandi, A  Fidalgo, S  Tonevitsky, AG  Dell, A  Volynski, KE  Ushkaryov, YA 
Citation: Silva JP, etal., Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):12113-8. doi: 10.1073/pnas.1019434108. Epub 2011 Jul 1.
Pubmed: (View Article at PubMed) PMID:21724987
DOI: Full-text: DOI:10.1073/pnas.1019434108

Latrophilin 1 (LPH1), a neuronal receptor of alpha-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 approximately 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.

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CRRD ID: 8553824
Created: 2014-05-08
Species: All species
Last Modified: 2014-05-08
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.