RT Journal Article
SR Electronic
T1 ATP Binding to Synaspsin IIa Regulates Usage and Clustering of Vesicles in Terminals of Hippocampal Neurons
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 985
OP 998
DO 10.1523/JNEUROSCI.0944-14.2015
VO 35
IS 3
A1 Shulman, Yoav
A1 Stavsky, Alexandra
A1 Fedorova, Tatiana
A1 Mikulincer, Dan
A1 Atias, Merav
A1 Radinsky, Igal
A1 Kahn, Joy
A1 Slutsky, Inna
A1 Gitler, Daniel
YR 2015
UL http://www.jneurosci.org/content/35/3/985.abstract
AB Synaptic transmission is expensive in terms of its energy demands and was recently shown to decrease the ATP concentration within presynaptic terminals transiently, an observation that we confirm. We hypothesized that, in addition to being an energy source, ATP may modulate the synapsins directly. Synapsins are abundant neuronal proteins that associate with the surface of synaptic vesicles and possess a well defined ATP-binding site of undetermined function. To examine our hypothesis, we produced a mutation (K270Q) in synapsin IIa that prevents ATP binding and reintroduced the mutant into cultured mouse hippocampal neurons devoid of all synapsins. Remarkably, staining for synaptic vesicle markers was enhanced in these neurons compared with neurons expressing wild-type synapsin IIa, suggesting overly efficient clustering of vesicles. In contrast, the mutation completely disrupted the capability of synapsin IIa to slow synaptic depression during sustained 10 Hz stimulation, indicating that it interfered with synapsin-dependent vesicle recruitment. Finally, we found that the K270Q mutation attenuated the phosphorylation of synapsin IIa on a distant PKA/CaMKI consensus site known to be essential for vesicle recruitment. We conclude that ATP binding to synapsin IIa plays a key role in modulating its function and in defining its contribution to hippocampal short-term synaptic plasticity.