DOI: 10.5061/dryad.st621
title: Data from: Drosophila studies support a role for a presynaptic synaptotagmin mutation in a human congenital myasthenic syndrome

description: During chemical transmission, the function of synaptic proteins must be
 coordinated to efficiently release neurotransmitter. Synaptotagmin 2, the
 Ca2+ sensor for fast, synchronized neurotransmitter release at the human
 neuromuscular junction, has recently been implicated in a dominantly
 inherited congenital myasthenic syndrome associated with a non-progressive
 motor neuropathy. In one family, a proline residue within the C2B
 Ca2+-binding pocket of synaptotagmin is replaced by a leucine. The
 functional significance of this residue has not been investigated
 previously. Here we show that in silico modeling predicts disruption of
 the C2B Ca2+-binding pocket, and we examine the in vivo effects of the
 homologous mutation in Drosophila. When expressed in the absence of native
 synaptotagmin, this mutation is lethal, demonstrating for the first time
 that this residue plays a critical role in synaptotagmin function. To
 achieve expression similar to human patients, the mutation is expressed in
 flies carrying one copy of the wild type synaptotagmin gene. We now show
 that Drosophila carrying this mutation developed neurological and
 behavioral manifestations similar to those of human patients and provide
 insight into the mechanisms underlying these deficits. Our Drosophila
 studies support a role for this synaptotagmin point mutation in disease
 etiology.
description: Fig2C_Blot3Original blot used to quantify Fig2CFig2C Blot2Original blot to quantify Fig2CFig2C_Blot2.pngFig2C_Blot1Original blot to quantify Fig2CFig2B_Blot2Original blot to quantify Fig2BFig2B_Blot1Original blot to quantify Fig2BFig2A_Blot2Original blot to quantify Fig2AFig2A_Blot1Original blot to quantify Fig2AFig2_2ARaw data values for Fig2A quantificationFig2_2BRaw data values for quantification of Fig2BFig2_2CRaw data values for Fig2C quantificationFig3_Fig 3 A,BRaw counts and percentages for lifespan of both control and experimental adult flies. Figure 3.Fig4_4B ControlRaw response amplitudes per fiber for control evoked responses. Figure 4B.Fig4_4B P-LRaw response amplitudes per fiber for experimental genotype evoked responses. Figure 4B.Fig4_4B STATSStatistical analysis for Fig4BFig4_4DRaw data values and statistical analysis for Fig 4DFig4_4ERaw data values and statistical analysis for Fig4E.Fig5_5ARaw data values and statistical analysis for Fig5A.Fig5_5BRaw data values for Fig5B.Fig5_5CRaw data values and statistical analysis for Fig5C.Fig5_5DRaw data values and statistical analysis for Fig5D.Fig6_6B ControlRaw and normalized data values for control in Fig6B.Fig6_6B P-LRaw and normalized data values for experimental gentoype in Fig6B.Fig7_7B ControlRaw and normalized data values for control in Fig7B.Fig7_7B P-LRaw and normalized data values for experimental gentoype in Fig7B.Fig8_8C Male control averagesRaw data values and averages for control in Fig8CFig8_8C Male P-L averagesRaw data values and averages for experimental genotype in Fig8CFig8_8A Female Control averagesRaw data values and averages for control in Fig8AFig8_8A Female P-L averagesRaw data values and averages for experimental genotype in Fig8AFig8_8B TTESTRaw data and statistical analysis for Fig8BFig8_8D TTESTRaw data and statistical analysis for Fig8D.Fig9 Fig9A-BRaw values and averages for Fig 9A-BFig9_Fig9A-B.csvFig9_BinningAverages for Fig 9 binned into 1-minute intervals