A trimeric protein complex functions as a synaptic chaperone machine.
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.
Tobaben
S
S
Max-Planck-Institute for Experimental Medicine, 37075 Göttingen, Germany.
Thakur
P
P
Fernández-Chacón
R
R
Südhof
T C
TC
Rettig
J
J
Stahl
B
B
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001923:Brain Chemistry; D002352:Carrier Proteins; D002478:Cells, Cultured; D005089:Exocytosis / Q000502:physiology*; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D046911:Macromolecular Substances; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D018832:Molecular Chaperones / Q000737:chemistry / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000737:chemistry / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494372:Hspa8 protein, mouse; C494373:Hspa8 protein, rat; D046911:Macromolecular Substances; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D011506:Proteins; C512694:Sgta protein, rat; C088460:cysteine string protein; D000255:Adenosine Triphosphate