Structural domains involved in the regulation of transmitter release by synapsins
Nairn, Angus C.
Czernik, Andrew J.
Augustine, George J.
MetadataShow full item record
Synapsins are a family of neuron-specific phosphoproteins that regulate neurotransmitter release by associating with synaptic vesicles. Synapsins consist of a series of conserved and variable structural domains of unknown function. We performed a systematic structure-function analysis of the various domains of synapsin by assessing the actions of synapsin fragments on neurotransmitter release, presynaptic ultrastructure, and the biochemical interactions of synapsin. Injecting a peptide derived from domain A into the squid giant presynaptic terminal inhibited neurotransmitter release in a phosphorylation-dependent manner. This peptide had no effect on vesicle pool size, synaptic depression, or transmitter release kinetics. In contrast, a peptide fragment from domain C reduced the number of synaptic vesicles in the periphery of the active zone and increased the rate and extent of synaptic depression. This peptide also slowed the kinetics of neurotransmitter release without affecting the number of docked vesicles. The domain C peptide, as well as another peptide from domain E that is known to have identical effects on vesicle pool size and release kinetics, both specifically interfered with the binding of synapsins to actin but not with the binding of synapsins to synaptic vesicles. This suggests that both peptides interfere with release by preventing interactions of synapsins with actin. Thus, interactions of domains C and E with the actin cytoskeleton may allow synapsins to perform two roles in regulating release, whereas domain A has an actin-independent function that regulates transmitter release in a phosphorylation-sensitive manner.
Author Posting. © Society for Neuroscience, 2005. This article is posted here by permission of Society for Neuroscience for personal use, not for redistribution. The definitive version was published in Journal of Neuroscience 25 (2005): 2658-2669, doi:10.1523/JNEUROSCI.4278-04.2005.
Suggested CitationArticle: Hilfiker, Sabine, Benfenati, Fabio, Doussau, Frederic, Nairn, Angus C., Czernik, Andrew J., Augustine, George J., Greengard, Paul, "Structural domains involved in the regulation of transmitter release by synapsins", Journal of Neuroscience 25 (2005): 2658-2669, DOI:10.1523/JNEUROSCI.4278-04.2005, https://hdl.handle.net/1912/2960
Showing items related by title, author, creator and subject.
Zuchero, J. Bradley; Belin, Brittany J.; Mullins, R. Dyche (American Society for Cell Biology, 2012-01-19)Junction-mediating and regulatory protein (JMY) is a regulator of both transcription and actin filament assembly. In response to DNA damage, JMY accumulates in the nucleus and promotes p53-dependent apoptosis. JMY's ...
Release of ecologically relevant metabolites by the cyanobacterium Synechococcus elongatus CCMP 1631 Fiore, Cara L.; Longnecker, Krista; Kido Soule, Melissa C.; Kujawinski, Elizabeth B. (2015-04-30)Photoautotrophic plankton in the surface ocean release organic compounds that fuel secondary production by heterotrophic bacteria. Here we show that an abundant marine cyanobacterium, Synechococcus elongatus, contributes ...
Montgomery, Ellyn T. (Woods Hole Oceanographic Institution, 1998-03)On two recent cruises January 1996 and February 1997) aboard the R/V Seward Johnson, scientists from the Woods Hole Oceanographic Institution studied the deep mixing processes in the Brazil Basin. Two instrument systems ...