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    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
8809837 - Pharmacological properties of peripherally induced postsynaptic potentials in bulbar re...
18722467 - Physiological consequences of selective suppression of synaptic transmission in develop...
1359477 - Epsps in rat neocortical pyramidal neurones in vitro are prolonged by nmda receptor-med...
21796527 - Analysis of nuclear receptor acetylation.
10779697 - Kappa-opioid agonist stimulated regional distribution of [(35)s]gtpgammas binding in bu...
11077037 - Angiotensin ii type 1 receptor antagonists. why do some of them produce insurmountable ...
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
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Calcium Signaling / physiology*
Cloning, Molecular
Hippocampus / metabolism*,  physiology
Immunoblotting
Microscopy, Immunoelectron
Molecular Sequence Data
Nerve Tissue Proteins / genetics*,  metabolism*
Rats
Receptors, Cell Surface / genetics*,  metabolism*
Receptors, Peptide / metabolism*
Sequence Analysis, DNA
Synapses / metabolism*
Synaptic Transmission / physiology*
Grant Support
ID/Acronym/Agency:
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
Chemical
Reg. No./Substance:
0/Nerve Tissue Proteins; 0/Odz2 protein, rat; 0/Receptors, Cell Surface; 0/Receptors, Peptide; 0/alpha-latrotoxin receptor
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Attenuation correction methods suitable for brain imaging with a PET/MRI scanner: a comparison of ti...
Next Document:  The purinergic G protein-coupled receptor 6 inhibits effector T cell activation in allergic pulmonar...