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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1998-2-12
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pubmed:abstractText |
alpha-Latrotoxin is a potent neurotoxin from black widow spider venom that binds to presynaptic receptors and causes massive neurotransmitter release. A surprising finding was the biochemical description of two distinct cell surface proteins that bind alpha-latrotoxin with nanomolar affinities; Neurexin I alpha binds alpha-latrotoxin in a Ca(2+)-dependent manner, and CIRL/latrophilin binds in a Ca(2+)-independent manner. We have now generated and analyzed mice that lack neurexin I alpha to test its importance in alpha-latrotoxin action. alpha-Latrotoxin binding to brain membranes from mutant mice was decreased by almost 50% compared with wild type membranes; the decrease was almost entirely due to a loss of Ca(2+)-dependent alpha-latrotoxin binding sites. In cultured hippocampal neurons, alpha-latrotoxin was still capable of activating neurotransmission in the absence of neurexin I alpha. Direct measurements of [3H]glutamate release from synaptosomes, however, showed a major decrease in the amount of release triggered by alpha-latrotoxin in the presence of Ca2+. Thus neurexin I alpha is not essential for alpha-latrotoxin action but contributes to alpha-latrotoxin action when Ca2+ is present. Viewed as a whole, our results show that mice contain two distinct types of alpha-latrotoxin receptors with similar affinities and abundance but different properties and functions. The action of alpha-latrotoxin may therefore be mediated by independent parallel pathways, of which the CIRL/latrophilin pathway is sufficient for neurotransmitter release, whereas the neurexin I alpha pathway contributes to the Ca(2+)-dependent action of alpha-latrotoxin.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Peptide,
http://linkedlifedata.com/resource/pubmed/chemical/Spider Venoms,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-latrotoxin,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-latrotoxin receptor,
http://linkedlifedata.com/resource/pubmed/chemical/neurexophilin
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1705-10
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9430716-Alternative Splicing,
pubmed-meshheading:9430716-Animals,
pubmed-meshheading:9430716-Brain,
pubmed-meshheading:9430716-Calcium,
pubmed-meshheading:9430716-Cell Membrane,
pubmed-meshheading:9430716-Chromosome Mapping,
pubmed-meshheading:9430716-Glutamic Acid,
pubmed-meshheading:9430716-Glycoproteins,
pubmed-meshheading:9430716-Mice,
pubmed-meshheading:9430716-Mice, Knockout,
pubmed-meshheading:9430716-Nerve Tissue Proteins,
pubmed-meshheading:9430716-Neuropeptides,
pubmed-meshheading:9430716-Receptors, Peptide,
pubmed-meshheading:9430716-Spider Venoms,
pubmed-meshheading:9430716-Synaptic Transmission,
pubmed-meshheading:9430716-Synaptosomes
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pubmed:year |
1998
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pubmed:articleTitle |
Neurexin I alpha is a major alpha-latrotoxin receptor that cooperates in alpha-latrotoxin action.
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pubmed:affiliation |
Max-Planck-Institut für Experimentelle Medizin, Göttingen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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