TY - JOUR T1 - <em>Drosophila </em>Stoned Proteins Regulate the Rate and Fidelity of Synaptic Vesicle Internalization JF - The Journal of Neuroscience JO - J. Neurosci. SP - 3034 LP - 3044 DO - 10.1523/JNEUROSCI.21-09-03034.2001 VL - 21 IS - 9 AU - Daniel T. Stimson AU - Patricia S. Estes AU - Sujata Rao AU - K. S. Krishnan AU - Leonard E. Kelly AU - Mani Ramaswami Y1 - 2001/05/01 UR - http://www.jneurosci.org/content/21/9/3034.abstract N2 - At an initial step during synaptic vesicle recycling, dynamin and adaptor proteins mediate the endocytosis of synaptic vesicle components from the plasma membrane. StonedA and stonedB, novel synaptic proteins encoded by a single Drosophila gene, have predicted structural similarities to adaptors and other proteins implicated in endocytosis. Here, we test possible roles of the stoned proteins in synaptic vesicle internalization via analyses of third instar larval neuromuscular synapses in two Drosophila stoned (stn) mutants,stnts andstn8P1. Both mutations reduce presynaptic levels of stonedA and stonedB, althoughstnts has relatively weak effects. The mutations cause retention of synaptic vesicle proteins on the presynaptic plasma membrane but do not alter the levels or distribution of endocytosis proteins, dynamin, α-adaptin, and clathrin. In addition, stn8P1 mutants exhibit depletion and enlargement of synaptic vesicles. To determine whether these defects arise from altered synaptic vesicle endocytosis or from defects in synaptic vesicle biogenesis, we implemented new methods to assess directly the efficiency of synaptic vesicle recycling and membrane internalization at Drosophila nerve terminals. Behavioral and electrophysiological analyses indicate thatstnts, an allele with normal evoked release and synaptic vesicle number, enhances defects in synaptic vesicle recycling shown by Drosophila shits mutants. A dye uptake assay demonstrates that slow synaptic vesicle recycling instnts is accompanied by a reduced rate of synaptic vesicle internalization after exocytosis. These observations are consistent with a model in which stonedA and stonedB act to facilitate the internalization of synaptic vesicle components from the plasma membrane. ER -