Profiling Synaptic Proteins Identifies Regulators of Insulin Secretion and Lifespan

Overview

Journal PLoS Genet

Specialty Genetics

Date 2008 Dec 2

PMID 19043554

Citations 63

Authors

QueeLim Chng

Derek Sieburth

Joshua M Kaplan

Affiliations

Soon will be listed here.

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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References

Vashlishan A, Madison J, Dybbs M, Bai J, Sieburth D, Chng Q . An RNAi screen identifies genes that regulate GABA synapses. Neuron. 2008; 58(3):346-61. DOI: 10.1016/j.neuron.2008.02.019. View

McEwen J, Madison J, Dybbs M, Kaplan J . Antagonistic regulation of synaptic vesicle priming by Tomosyn and UNC-13. Neuron. 2006; 51(3):303-15. DOI: 10.1016/j.neuron.2006.06.025. View

Renden R, Berwin B, Davis W, Ann K, Chin C, Kreber R . Drosophila CAPS is an essential gene that regulates dense-core vesicle release and synaptic vesicle fusion. Neuron. 2001; 31(3):421-37. DOI: 10.1016/s0896-6273(01)00382-8. View

Dittman J, Kaplan J . Factors regulating the abundance and localization of synaptobrevin in the plasma membrane. Proc Natl Acad Sci U S A. 2006; 103(30):11399-404. PMC: 1544097. DOI: 10.1073/pnas.0600784103. View

Nagai T, Ibata K, Park E, Kubota M, Mikoshiba K, Miyawaki A . A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applications. Nat Biotechnol. 2001; 20(1):87-90. DOI: 10.1038/nbt0102-87. View

Sieburth D, Madison J, Kaplan J . PKC-1 regulates secretion of neuropeptides. Nat Neurosci. 2006; 10(1):49-57. DOI: 10.1038/nn1810. View

Dai Y, Taru H, Deken S, Grill B, Ackley B, Nonet M . SYD-2 Liprin-alpha organizes presynaptic active zone formation through ELKS. Nat Neurosci. 2006; 9(12):1479-87. DOI: 10.1038/nn1808. View

Sieburth D, Chng Q, Dybbs M, Tavazoie M, Kennedy S, Wang D . Systematic analysis of genes required for synapse structure and function. Nature. 2005; 436(7050):510-7. DOI: 10.1038/nature03809. View

Schuldiner M, Collins S, Thompson N, Denic V, Bhamidipati A, Punna T . Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile. Cell. 2005; 123(3):507-19. DOI: 10.1016/j.cell.2005.08.031. View

10.

Patel M, Lehrman E, Poon V, Crump J, Zhen M, Bargmann C . Hierarchical assembly of presynaptic components in defined C. elegans synapses. Nat Neurosci. 2006; 9(12):1488-98. PMC: 3917495. DOI: 10.1038/nn1806. View

11.

Huh W, Falvo J, Gerke L, Carroll A, Howson R, Weissman J . Global analysis of protein localization in budding yeast. Nature. 2003; 425(6959):686-91. DOI: 10.1038/nature02026. View

12.

Weimer R, Gracheva E, Meyrignac O, Miller K, Richmond J, Bessereau J . UNC-13 and UNC-10/rim localize synaptic vesicles to specific membrane domains. J Neurosci. 2006; 26(31):8040-7. PMC: 3874421. DOI: 10.1523/JNEUROSCI.2350-06.2006. View

13.

de Hoon M, Imoto S, Nolan J, Miyano S . Open source clustering software. Bioinformatics. 2004; 20(9):1453-4. DOI: 10.1093/bioinformatics/bth078. View

14.

Mathews E, Garcia E, Santi C, Mullen G, Thacker C, Moerman D . Critical residues of the Caenorhabditis elegans unc-2 voltage-gated calcium channel that affect behavioral and physiological properties. J Neurosci. 2003; 23(16):6537-45. PMC: 6740628. View

15.

Balklava Z, Pant S, Fares H, Grant B . Genome-wide analysis identifies a general requirement for polarity proteins in endocytic traffic. Nat Cell Biol. 2007; 9(9):1066-73. DOI: 10.1038/ncb1627. View

16.

Yao I, Takagi H, Ageta H, Kahyo T, Sato S, Hatanaka K . SCRAPPER-dependent ubiquitination of active zone protein RIM1 regulates synaptic vesicle release. Cell. 2007; 130(5):943-57. PMC: 3049808. DOI: 10.1016/j.cell.2007.06.052. View

17.

Martin T . Tuning exocytosis for speed: fast and slow modes. Biochim Biophys Acta. 2003; 1641(2-3):157-65. DOI: 10.1016/s0167-4889(03)00093-4. View

18.

Apfeld J, Kenyon C . Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature. 2000; 402(6763):804-9. DOI: 10.1038/45544. View

19.

Bennett D, Bailyes E, Nielsen E, Guest P, Rutherford N, Arden S . Identification of the type 2 proinsulin processing endopeptidase as PC2, a member of the eukaryote subtilisin family. J Biol Chem. 1992; 267(21):15229-36. View

20.

Crump J, Zhen M, Jin Y, Bargmann C . The SAD-1 kinase regulates presynaptic vesicle clustering and axon termination. Neuron. 2001; 29(1):115-29. DOI: 10.1016/s0896-6273(01)00184-2. View