An updated reappraisal of synapsins: structure, function and role in neurological and psychiatric disorders

Synapsins (Syns) are phosphoproteins strongly involved in neuronal development and neurotransmitter release. Three distinct genes SYN1, SYN2 and SYN3, with elevated evolutionary conservation, have been described to encode for Synapsin I, Synapsin II and Synapsin III, respectively. Syns display a series of common features, but also exhibit distinctive localization, expression pattern, posttranslational modifications (PTM). These characteristics enable their interaction with other synaptic proteins, membranes and cytoskeletal components, which is essential for the proper execution of their multiple functions in neuronal cells. These include the control of synapse formation and growth, neuron maturation and renewal, as well as synaptic vesicle mobilization, docking, fusion, recycling. Perturbations in the balanced expression of Syns, alterations of their PTM, mutations and polymorphisms of their encoding genes induce severe dysregulations in brain networks functions leading to the onset of psychiatric or neurological disorders. This review presents what we have learned since the discovery of Syn I in 1977, providing the state of the art on Syns structure, function, physiology and involvement in central nervous system disorders.

Automated summary

Synapsins are phosphoproteins involved in neuronal development and neurotransmitter release, with multiple functions in synaptic formation, vesicle mobilization, and recycling. Dysregulation in their expression, modifications, or encoding genes can lead to brain network dysfunction and psychiatric or neurological disorders. This review provides the latest information on Syns structure, function, physiology, and their role in central nervous system disorders.