Synapsin IIa function is regulated by an ATP binding site

The synapsins are neuron-specific proteins mostly known
for their capability to cluster synaptic vesicles and to control
vesicle movement between adjacent en-passant synapses.
Early studies revealed various sites that were suggested to
S114 J Mol Neurosci (2013) 51 (Suppl 1):S1–S135
regulate the activity of synapsin I, the first synapsin to be
described. Although synapsin IIa was recently shown to be
the dominant member of this family, at least in small glutamatergic synapses, its regulation has not been studied in any
detail to date. All members of the synapsin family bind ATP
at a well-conserved site in their central "C" domain. Intriguingly, ATP binding is differentially regulated by calcium
ions, suggesting a physiological function. Nevertheless, the
significance of ATP binding has not been investigated in the
context of neurotransmission. To study this question, we
measured the rescue of synaptic depression in autaptic neurons lacking all synapsins by the over expression of either
exogenous wild type synapsin IIa or synapsin IIa carrying a
mutation (K270A) which prevents ATP binding. We found
that K270A-synapsin IIa only partially rescues synaptic
depression. All results support a role for ATP in regulating
synapsin activity in synapses in-vivo.