Profiling synaptic proteins identifies regulators of insulin secretion and lifespan

• Published in: PLoS genetics 2008-11, Vol.4 (11), p.e1000283-e1000283
• Main Authors: Ch'ng, Queelim, Sieburth, Derek, Kaplan, Joshua M
• Format: Article
• Language: English
• Subjects: Animals; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cells; Cellular proteins; Developmental Biology/Aging; Gene Expression Profiling; Genetic aspects; Genetics and Genomics; Genetics and Genomics/Bioinformatics; Insulin - metabolism; Insulin Secretion; Insulin-like growth factor 1; Insulin-like growth factors; Longevity - genetics; Membrane Proteins - analysis; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metabolic disorders; Neural transmission; Neuroscience/Neuronal and Glial Cell Biology; Neuroscience/Neuronal Signaling Mechanisms; Physiological aspects; Presynaptic Terminals - metabolism; Proteins; Signal Transduction; Somatomedins - metabolism; Synapses - genetics; Synapses - physiology
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1000283

Cells are organized into distinct compartments to perform specific tasks with spatial precision. In neurons, presynaptic specializations are biochemically complex subcellular structures dedicated to neurotransmitter secretion. Activity-dependent changes in the abundance of presynaptic proteins are thought to endow synapses with different functional states; however, relatively little is known about the rules that govern changes in the composition of presynaptic terminals. We describe a genetic strategy to systematically analyze protein localization at Caenorhabditis elegans presynaptic specializations. Nine presynaptic proteins were GFP-tagged, allowing visualization of multiple presynaptic structures. Changes in the distribution and abundance of these proteins were quantified in 25 mutants that alter different aspects of neurotransmission. Global analysis of these data identified novel relationships between particular presynaptic components and provides a new method to compare gene functions by identifying shared protein localization phenotypes. Using this strategy, we identified several genes that regulate secretion of insulin-like growth factors (IGFs) and influence lifespan in a manner dependent on insulin/IGF signaling.