Synapsin Isoforms and Synaptic Vesicle Trafficking

Abstract

Synapsins were the first presynaptic proteins identified and have served as the flagship of the presynaptic protein field. Here we review recent studies demonstrating that different members of the synapsin family play different roles at presynaptic terminals employing different types of synaptic vesicles. The structural underpinnings for these functions are just beginning to be understood and should provide a focus for future efforts.

Keywords: neurotransmitter release; presynaptic terminals; synapsins; synaptic vesicles; vesicle trafficking.

Fig. 1.

Domain model of the vertebrate synapsin family. Experimentally determined phosphorylation sites within synapsin Ia are indicated, along with the kinases that phosphorylate these sites. Scale at bottom shows amino acid number.

Fig. 2.

Effect of synapsin deletion on neurotransmitter release at different synapses and chromaffin cells. (A) Neurotransmitter release at a glutamatergic synapse. Left –excitatory postsynaptic currents (EPSCs) evoked by single stimuli, recorded from autaptic cultures of hippocampal excitatory neurons from synapsin triple wild-type (TWT) and triple knock-out (TKO) mice. Right - kinetics of synaptic depression, evident as a decline in mean amplitude of EPSCs evoked by trains of stimuli (500 at 10 Hz). Replotted from data in Gitler et al. (2004b). (B) Neurotransmitter release at a GABAergic synapse. Left – inhibitory postsynaptic currents (IPSCs) evoked by single stimuli, recorded from autaptic cultures of hippocampal inhibitory neurons from TWT and TKO mice. Right - kinetics of synaptic depression, evident as a decline in mean amplitude of IPSCs evoked by trains of stimuli (500 at 10 Hz). Replotted from data in Gitler et al. (2004b). (C) Catecholamine release from cultured adrenal chromaffin cells. Left - Representative amperometric measurements of exocytotic discharge of catecholamine (spikes) from TWT and TKO cells in response to treatment with a high-potassium (60 mM K⁺) during times indicated by horizontal bars. Right - comparison of number of catecholamine release spikes evoked in TWT and TKO cells. Replotted from data in Villanueva et al. (2006). (D) Dopamine (DA) release evoked by a single electrical stimulus (vertical black line) in striatal brain slices from TWT and TKO mice. Left - Representative responses. Right - mean [DA] measured in slices from each genotype (right). Replotted from data in Kile et al. (2010). (E) Representative traces of serotonin release evoked by electrical stimulation (100 Hz, 20 pulses, black line) from substantia nigra in brain slices from TWT and TKO mice. Replotted from data in Kile et al. (2010).