Molecular chaperones and the regulation of neurotransmitter exocytosis.
Regulated neurotransmitter release depends on a precise sequence of events that lead to repeated cycles of exocytosis and endocytosis. These events are mediated by a series of molecular interactions among vesicular, plasma membrane, and cytosolic proteins. An emerging theme has been that molecular chaperones may guide the sequential restructuring of stable or transient protein complexes to promote a temporal and spatial regulation of the endo- and exocytotic machinery and to ensure a vectorial passage through the vesicle cycle. Chaperones, specialized for a few substrates, are ideally suited to participate in regulatory processes that require some molecular dexterity to rearrange conformational or oligomeric protein structures. This article emphasizes the significance of three molecular chaperone systems in regulated neurotransmitter release: the regulation of soluble NSF attachment protein receptor (SNARE) complexes by N-ethylmaleimide-sensitive factor (NSF) and the soluble NSF attachment protein (SNAP), the uncoating of clathrin-coated vesicles by the 70 kDa heat-shock cognate protein (Hsc70), and the regulation of SNARE complex-associated protein interactions by cysteine-string protein and Hsc70.
Zinsmaier
K E
KE
Department of Neuroscience, 234d Stemmler Hall, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6974, USA. zinsmaie@mail.med.upenn.edu
Bronk
P
P
D033942:Adaptor Proteins, Vesicular Transport; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D052066:N-Ethylmaleimide-Sensitive Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D002966:Clathrin; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D010750:Phosphoproteins; C110881:S-nitro-N-acetylpenicillamine; D050600:SNARE Proteins; D033921:Vesicular Transport Proteins; D000251:Adenosine Triphosphatases; D052066:N-Ethylmaleimide-Sensitive Proteins; D010396:Penicillamine