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

Silva, John Paul, Lelianova, Vera, Ermolyuk, Yaroslav S., Vysokov, Nickolai, Hitchen, Paul G., Berninghausen, Otto, Rahman, M. Atiqur, Zangrandi, Alice, Fidalgo, Sara, Tonevitsky, Alexandre G., and others. (2011) Latrophilin 1 and its endogenous ligand Lasso/teneurin-2 form a high-affinity transsynaptic receptor pair with signaling capabilities. Proceedings of the National Academy of Sciences, 108 (29). pp. 12113-12118. ISSN 1091-6490. (doi:10.1073/pnas.1019434108) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1073/pnas.1019434108

Abstract

Latrophilin 1 (LPH1), a neuronal receptor of ?-latrotoxin, is implicated in neurotransmitter release and control of presynaptic Ca2+. 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 Ca2+ 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 Ca2+ signals, which might affect synaptic functions.

Item Type: Article
DOI/Identification number: 10.1073/pnas.1019434108
Additional information: number of additional authors: 11;
Subjects: Q Science
R Medicine > RS Pharmacy and materia medica
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Stewart Brownrigg
Date Deposited: 07 Mar 2014 00:05 UTC
Last Modified: 29 May 2019 12:24 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/40391 (The current URI for this page, for reference purposes)
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