DRUSE

In a paper by QueeLim Ch’ng and colleagues, a genetic analysis of presynaptic structure in the worm Caenorhabditis elegans was described after measuring in vivo changes in the distribution of fluorescently tagged presynaptic proteins. Because changes in the abundance of presynaptic proteins often indicate different synaptic functional states, they developed a genetic strategy to systematically analyze protein localization at presynaptic structures by GFP-tagging. 25 mutants were observed showing different aspects of neurotransmission. Global analysis of these data identified novel relationships between particular presynaptic components. Moreover, they also identified several genes that regulate secretion of insulin-like growth factors (IGFs) from neurons, and showed that these genes regulate lifespan, a physiological function of IGF signaling.

Ch’ng Q, Sieburth D, Kaplan JM (2008) Profiling Synaptic Proteins Identifies Regulators of Insulin Secretion and Lifespan. PLoS Genet 4(11): e1000283. doi:10.1371/journal.pgen.1000283

Figure 6. Analysis of DCV accumulation in axons and insulin/IGF secretion. (A) XY plot comparing changes in the punctal fluorescence of SNB-1 synaptobrevin and INS-22 insulin/IGF. Two mutants with more prominent increases in INS-22 insulin/IGF than SNB-1 synaptobrevin are shown as solid orange circles. (B) Secreted INS-22 insulin/IGF expressed in motorneurons accumulates in coelomocytes. (C) Images of INS-22 insulin/IGF accumulation in coelomocytes in wild type and mutant animals. Scale bar, 5 µm. Below is shown the quantification of coelomocyte INS-22 insulin/IGF fluorescence. (D) Images of axonal INS-22 insulin/IGF in wild type animals and mutants with altered INS-22 insulin/IGF coelomocyte fluorescence. Scale bar, 5 µm. Below is shown the quantification of INS-22 insulin/IGF punctal fluorescence. In (C–D), * indicates p<0.05, ** indicates p<0.01, (Student’s T-Test compared to wild type). All error bars are ±SEM. Separate charts indicate data from separate sets of experiments.

Figure 7. Insulin/IGF secretion mutants show lifespan phenotypes. (A–F) Survival curves with indicated genotypes. * indicates significantly different lifespan from wild type (p<0.0001), † indicates significant suppression by daf-16 FOXO (p<0.0001), § indicates significant suppression by daf-2 InsR (p<0.0001), (Log Rank Test).