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Broadie Laboratory

The stoned proteins regulate synaptic vesicle recycling in the presynaptic terminal.

AUTHORS

Fergestad TT , Davis WS W S , Broadie K K . The Journal of neuroscience : the official journal of the Society for Neuroscience. 1999 7 15; 19(14). 5847-60

ABSTRACT

The Drosophila stoned locus was identified 25 years ago on the basis of stress-sensitive behavioral mutants (Grigliatti et al., 1973). The locus is dicistronic and encodes two distinct proteins, stoned A and stoned B, which are expressed specifically in presynaptic terminals at central and peripheral synapses. Several stoned mutant alleles cause embryonic lethality, suggesting that these proteins are essential for synaptic function. Physiological analyses at the stoned synapse reveal severe neurotransmission defects, including reduced and asynchronous neurotransmitter release and rapid fatigue after repetitive stimulation. At the EM level, stoned synapses show a depletion of synaptic vesicles and a concomitant increase in membrane-recycling intermediates. Mutant terminals also display a specific mislocalization of the synaptic vesicle protein synaptotagmin. These results suggest that the stoned proteins are essential for the recycling of synaptic vesicle membrane and are required for the proper sorting of synaptotagmin during endocytosis.

The Drosophila stoned locus was identified 25 years ago on the basis of stress-sensitive behavioral mutants (Grigliatti et al., 1973). The locus is dicistronic and encodes two distinct proteins, stoned A and stoned B, which are expressed specifically in presynaptic terminals at central and peripheral synapses. Several stoned mutant alleles cause embryonic lethality, suggesting that these proteins are essential for synaptic function. Physiological analyses at the stoned synapse reveal severe neurotransmission defects, including reduced and asynchronous neurotransmitter release and rapid fatigue after repetitive stimulation. At the EM level, stoned synapses show a depletion of synaptic vesicles and a concomitant increase in membrane-recycling intermediates. Mutant terminals also display a specific mislocalization of the synaptic vesicle protein synaptotagmin. These results suggest that the stoned proteins are essential for the recycling of synaptic vesicle membrane and are required for the proper sorting of synaptotagmin during endocytosis.

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