Two sites of action for synapsin domain E in regulating neurotransmitter release

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  • A Correction to this article was published on 01 August 1998

Abstract

Synapsins, a family of synaptic vesicle proteins, have been shown to regulate neurotransmitter release; the mechanism(s) by which they act are not fully understood. Here we have studied the role of domain E of synapsins in neurotransmitter release at the squid giant synapse. Two squid synapsin isoforms were cloned and found to contain a carboxy (C)-terminal domain homologous to domain E of the vertebrate a-type synapsin isoforms. Presynaptic injection of a peptide fragment of domain E greatly reduced the number of synaptic vesicles in the periphery of the active zone, and increased the rate and extent of synaptic depression, suggesting that domain E is essential for synapsins to regulate a reserve pool of synaptic vesicles. Domain E peptide had no effect on the number of docked synaptic vesicles, yet reversibly inhibited and slowed the kinetics of neurotransmitter release, indicating a second role for synapsins that is more intimately associated with the release process itself. Thus, synapsin domain E is involved in at least two distinct reactions that are crucial for exocytosis in presynaptic terminals.

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Figure 1: Identification and deduced primary structure of squid synapsins.
Figure 2: Domain E peptide inhibits neurotransmitter release.
Figure 3: Domain E peptide enhances synaptic depression, but has no effect on facilitation.
Figure 4: Domain E peptide decreases the number of synaptic vesicles.
Figure 5: Domain E peptide injection slows the kinetics of transmitter release.

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Acknowledgements

We thank A. Jeromin and J. Battey for providing the squid stellate ganglion library, E. Buchner for providing the monoclonal antibody against Drosophila synapsin, S. Huber for EM image analysis, and J. Crawford for peptide synthesis. We are grateful to R. Rottenfusser (Zeiss), P. Bent (Nikon), and M. Delay (Axon Instruments) for loan of equipment and technical support. We also thank B. Finch and E. Griggs for help with the artwork, and V. Pieribone, T. Ryan and L. Brodin for advice and critical reading of the manuscript. Supported by a Grass Fellowship to S.H., The National Alliance for Research in Schizophrenia and Affective Disorders and The New York Community Trust by DeWitt-Wallace to H.-T. K., and NIH grants to P.G. and G.J.A.

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Correspondence to Paul Greengard.

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Hilfiker, S., Schweizer, F., Kao, H. et al. Two sites of action for synapsin domain E in regulating neurotransmitter release. Nat Neurosci 1, 29–35 (1998) doi:10.1038/229

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