Abstract
Alpha-latrotoxin is a potent neurotoxin that triggers synaptic exocytosis. Surprisingly, two distinct neuronal receptors for alpha-latrotoxin have been described: CIRL/latrophilin 1 (CL1) and neurexin-1alpha. Alpha-latrotoxin is thought to trigger exocytosis by binding to CL1, while the role of neurexin 1alpha is uncertain. Using PC12 cells, we now demonstrate that neurexins indeed function as alpha-latrotoxin receptors that are at least as potent as CL1. Both alpha- and beta-neurexins represent autonomous alpha-latrotoxin receptors that are regulated by alternative splicing. Similar to CL1, truncated neurexins without intracellular sequences are fully active; therefore, neurexins and CL1 recruit alpha-latrotoxin but are not themselves involved in exocytosis. Thus, alpha-latrotoxin is unique among neurotoxins, because it utilizes two unrelated receptors, probably to amplify recruitment of alpha-latrotoxin to active sites.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alternative Splicing
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Animals
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Binding Sites
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Calcium / physiology
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Exocytosis / physiology
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Glycoproteins
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Immunoglobulin G / genetics
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nerve Tissue Proteins / physiology*
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Neuropeptides
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PC12 Cells
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Rats
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Receptors, Peptide / biosynthesis
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Receptors, Peptide / genetics
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Receptors, Peptide / metabolism
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Receptors, Peptide / physiology*
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Spider Venoms / metabolism*
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Transfection
Substances
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Glycoproteins
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Immunoglobulin G
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Nerve Tissue Proteins
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Neuropeptides
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Receptors, Peptide
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Recombinant Fusion Proteins
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Spider Venoms
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alpha-latrotoxin receptor
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neurexophilin
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neurexin Ibeta
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alpha-latrotoxin
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Calcium