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Profiling Synaptic Proteins Identifies Regulators of Insulin Secretion and Lifespan

Research output: Contribution to journalArticlepeer-review

QueeLim Ch'ng, Derek Sieburth, Joshua M. Kaplan

Original languageEnglish
Article numbere1000283
JournalPL o S Genetics
Volume4
Issue number11
Early online date28 Nov 2008
DOIs
Accepted/In press28 Oct 2008
E-pub ahead of print28 Nov 2008
PublishedNov 2008

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Abstract

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.

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