Abstract
We identify a chaperone complex composed of (1) the synaptic vesicle cysteine string protein (CSP), thought to function in neurotransmitter release, (2) the ubiquitous heat-shock protein cognate Hsc70, and (3) the SGT protein containing three tandem tetratricopeptide repeats. These three proteins interact with each other to form a stable trimeric complex that is located on the synaptic vesicle surface, and is disrupted in CSP knockout mice. The CSP/SGT/Hsc70 complex functions as an ATP-dependent chaperone that reactivates a denatured substrate. SGT overexpression in cultured neurons inhibits neurotransmitter release, suggesting that the CSP/SGT/Hsc70 complex is important for maintenance of a normal synapse. Taken together, our results identify a novel trimeric complex that functions as a synapse-specific chaperone machine.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / physiology
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Animals
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Brain Chemistry
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Carrier Proteins
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Cells, Cultured
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Exocytosis / physiology*
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HSC70 Heat-Shock Proteins
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HSP40 Heat-Shock Proteins
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HSP70 Heat-Shock Proteins / chemistry
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HSP70 Heat-Shock Proteins / physiology*
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Hippocampus / cytology
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Macromolecular Substances
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Male
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Membrane Proteins / chemistry
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Membrane Proteins / deficiency
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Membrane Proteins / genetics
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Membrane Proteins / physiology*
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Mice
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Mice, Knockout
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Models, Biological
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Molecular Chaperones / chemistry
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Molecular Chaperones / physiology*
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / physiology*
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Neurotransmitter Agents / metabolism*
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Protein Binding
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Protein Folding
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Proteins / chemistry
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Proteins / physiology*
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Rats
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Rats, Wistar
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Synaptic Transmission / physiology*
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Synaptic Vesicles / chemistry
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Synaptic Vesicles / metabolism*
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Two-Hybrid System Techniques
Substances
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Carrier Proteins
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HSC70 Heat-Shock Proteins
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HSP40 Heat-Shock Proteins
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HSP70 Heat-Shock Proteins
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Hspa8 protein, mouse
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Hspa8 protein, rat
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Macromolecular Substances
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Membrane Proteins
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Molecular Chaperones
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Nerve Tissue Proteins
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Neurotransmitter Agents
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Proteins
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Sgta protein, rat
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cysteine string protein
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Adenosine Triphosphate