Synapsins and synaptic vesicle storage

The synapsins constitute a family of evolutionarily conserved neuronal phosphoproteins associated with the cytosolic surface of synaptic vesicles. In mammals, the family comprises three members encoded by distinct genes that give rise to various splicing isoforms. In the central nervous system, the vast majority of neurons expresses at least one synapsin isoform. However, the functions of these proteins are not fully understood to date. Given their ability to bind both the vesicular membrane and actin filaments in a phosphorylation-dependent manner, the classical role attributed to synapsins is the reversible anchorage of synaptic vesicles to the cytoskeletal matrix present in the presynaptic terminal. However, recent evidences suggest the implication of synapsins in other aspects of the synaptic vesicle life cycle, such as docking, fusion and recycling. Genetic manipulation of synapsins in various in vitro and in vivo models has proved that they are dispensable for the proper development of functional neuronal networks but are essential modulators of synaptic neurotransmission and play differential roles at excitatory and inhibitory synapses. Indeed, mice lacking synapsins are viable and do not display gross brain abnormalities but exhibit generalised epileptic seizures as well as autism-related behavioural abnormalities. Consistently, several mutations have been identified in SYN1 and SYN2 genes in patients affected by epilepsy and/or autism spectrum disorders. This chapter overviews the current knowledge about synapsin structure and function in the modulation of synaptic vesicle release, as well as the mechanisms leading to synaptic pathology when their properties are altered.