Two sites of action for synapsin domain E in regulating neurotransmitter release.
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.
Hilfiker
S
S
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, New York 10021, USA.
Schweizer
F E
FE
Kao
H T
HT
Czernik
A J
AJ
Greengard
P
P
Augustine
G J
GJ
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D003001:Cloning, Molecular; D049832:Decapodiformes; D007536:Isomerism; D007700:Kinetics; D008969:Molecular Sequence Data; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics* / Q000502:physiology*; D016704:Synapsins / Q000235:genetics* / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology
D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D016704:Synapsins