Phosphorylation of synapsin domain A is required for post-tetanic potentiation.
Post-tetanic potentiation (PTP) is a form of homosynaptic plasticity important for information processing and short-term memory in the nervous system. The synapsins, a family of synaptic vesicle (SV)-associated phosphoproteins, have been implicated in PTP. Although several synapsin functions are known to be regulated by phosphorylation by multiple protein kinases, the role of individual phosphorylation sites in synaptic plasticity is poorly understood. All the synapsins share a phosphorylation site in the N-terminal domain A (site 1) that regulates neurite elongation and SV mobilization. Here, we have examined the role of phosphorylation of synapsin domain A in PTP and other forms of short-term synaptic enhancement (STE) at synapses between cultured Helix pomatia neurons. To this aim, we cloned H. pomatia synapsin (helSyn) and overexpressed GFP-tagged wild-type helSyn or site-1-mutant helSyn mutated in the presynaptic compartment of C1-B2 synapses. We found that PTP at these synapses depends both on Ca2+/calmodulin-dependent and cAMP-dependent protein kinases, and that overexpression of the non-phosphorylatable helSyn mutant, but not wild-type helSyn, specifically impairs PTP, while not altering facilitation and augmentation. Our findings show that phosphorylation of site 1 has a prominent role in the expression of PTP, thus defining a novel role for phosphorylation of synapsin domain A in short-term homosynaptic plasticity.
Fiumara
Ferdinando
F
Department of Neuroscience, University of Torino, Corso Raffaello 30, 10125 Torino, Italy. ferdinando.fiumara@unito.it
Milanese
Chiara
C
Corradi
Anna
A
Giovedì
Silvia
S
Leitinger
Gerd
G
Menegon
Andrea
A
Montarolo
Pier Giorgio
PG
Benfenati
Fabio
F
Ghirardi
Mirella
M
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015870:Gene Expression; D006372:Helix, Snails / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology*; D009154:Mutation; D009473:Neuronal Plasticity / Q000502:physiology*; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D016704:Synapsins / Q000235:genetics / Q000378:metabolism*
D016704:Synapsins; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases