Cysteine-String Protein’s Role at Synapses

Abstract

Accumulating evidence illustrates the significance of chaperone systems for the regulation and maintenance of neuronal and synaptic function. The significance of synaptic chaperones is best illustrated by cysteine-string protein (CSP), a member of the DnaJ/Hsp40 family of Hsp70/Hsc70 co-chaperones. CSP recruits the ubiquitous chaperone Hsc70 to synaptic vesicles forming a chaperone complex that maintains synaptic function and prevents neurodegeneration. Here, we summarize studies that demonstrate CSP's neuroprotective role for synaptic function and discuss insights into its possible clientele (the proteins whose function it facilitates). General IntroductionSynaptic transmission occurs at highly specialized cell-cell contact sites, termed synapses. In the presynaptic axon terminal, quantal packages of neurotransmitter are stored in synaptic vesicles. Regulated neurotransmitter release is initiated by a depolarization-dependent Ca 2+ influx through voltage-gated Ca 2+ channels that triggers the fusion of synaptic vesicles with the presynaptic membrane releasing neurotransmitter into the synaptic cleft. In turn, activation of specific neurotransmitter receptors in the postsynaptic cell membrane induces a postsynaptic response in less than 100 ms after the presynaptic trigger. After exocytosis, synaptic vesicle membranes and proteins are rapidly recaptured and locally recycled ensuring that synapses can faithfully sustain transmitter release during prolonged periods of high nerve activity.Presynaptic terminals resemble specialized secretory machines that exhibit an unparalleled autonomy and durability. Both Ca 2+ signaling and synaptic vesicle fusion are driven by a series of protein-protein and protein-lipid interactions that involve a complex interplay among a specialized set of synaptic proteins and the