A Trimeric Protein Complex Functions as a Synaptic Chaperone Machine

Neuron. 2001 Sep 27;31(6):987-99. doi: 10.1016/s0896-6273(01)00427-5.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / physiology
  • Animals
  • Brain Chemistry
  • Carrier Proteins
  • Cells, Cultured
  • Exocytosis / physiology*
  • HSC70 Heat-Shock Proteins
  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / chemistry
  • HSP70 Heat-Shock Proteins / physiology*
  • Hippocampus / cytology
  • Macromolecular Substances
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / physiology*
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / physiology*
  • Neurotransmitter Agents / metabolism*
  • Protein Binding
  • Protein Folding
  • Proteins / chemistry
  • Proteins / physiology*
  • Rats
  • Rats, Wistar
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / chemistry
  • Synaptic Vesicles / metabolism*
  • Two-Hybrid System Techniques

Substances

  • Carrier Proteins
  • HSC70 Heat-Shock Proteins
  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Hspa8 protein, mouse
  • Hspa8 protein, rat
  • Macromolecular Substances
  • Membrane Proteins
  • Molecular Chaperones
  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Proteins
  • Sgta protein, rat
  • cysteine string protein
  • Adenosine Triphosphate