ESSENTIAL FUNCTIONS OF SYNAPSIN-I AND SYNAPSIN-II IN SYNAPTIC VESICLEREGULATION

SYNAPTIC vesicles are coated by synapsins, phosphoproteins that accoun t for 9% of the vesicle protein(1-3). To analyse the functions of thes e proteins, we have studied knockout mice lacking either synapsin I, s ynapsin II, or both. Mice lacking synapsins are viable and fertile wit h no gross anatomical abnormalities, but experience seizures with a fr equency proportional to the number of mutant alleles. Synapsin-II and double knockouts, but not synapsin-I knockouts, exhibit decreased post -tetanic potentiation and severe synaptic depression upon repetitive s timulation. Intrinsic synaptic-vesicle membrane proteins, but not peri pheral membrane proteins or other synaptic proteins, are slightly decr eased in individual knockouts and more severely reduced in double knoc kouts, as is the number of synaptic vesicles. Thus synapsins are not r equired for neurite outgrowth, synaptogenesis or the basic mechanics o f synaptic vesicle traffic, but are essential for accelerating this tr affic during repetitive stimulation. The phenotype of the synapsin kno ckouts could be explained either by deficient recruitment of synaptic vesicles to the active zone, or by impaired maturation of vesicles at the active zone, both of which could lead to a secondary destabilizati on of synaptic vesicles.