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. 2007 Dec 15;23(1):21–29. doi: 10.1007/s12264-007-0003-4

Involvement of genes required for synaptic function in aging control in C. elegans

突触功能必需基因参与线虫衰老的调控

Lu-Lu Shen 1,2, Yang Wang 1,2, Da-Yong Wang 1,2,✉
PMCID: PMC5500772  PMID: 17592521

Abstract

Objective

To identify new genes required for neurosecretory control of aging in C. elegans.

Methods

In view of the importance of nervous system in aging regulation, we performed the screen for genes involved in the aging regulation from genetic loci encoding synaptic proteins by lifespan assay and accumulation of lipofuscin autofluorescence. We further investigated the dauer formation phenotypes of their corresponding mutants and whether they were possibly up-regulated by the insulin-like signaling pathway.

Results

The genetic loci of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd-2, snb-1, ric-4, nrx-1, unc-13, sbt-1 and unc-64 might be involved in the aging control. In addition, functions of unc-10, syd-2, hlb-1, dlk-1, mkk-4, scd-2, snb-1, ric-4 and nrx-1 in regulating aging may be opposite to those of unc-13, sbt-1 and unc-64. The intestinal autofluorescence assay further indicated that the identified long-lived and short-lived mutants were actually due to the suppressed or accelerated aging. Among the identified genes, syd-2, hlb-1, mkk-4, scd-2, snb-1, ric-4 and unc-64 were also involved in the control of dauer formation. Moreover, daf-2 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, ric-4, sbt-1, rpm-1, unc-10, dlk-1 and unc-13. The daf-16 mutation positively regulated the expression of syd-2 and hlb-1, and negatively regulated the expression of mkk-4, nrx-1, sbt-1, rpm-1, unc-10, dlk-1 and unc-13.

Conclusion

These data suggest the possibly important status of the synaptic transmission to the animal’s life-span control machinery, as well as the dauer formation control.

Keywords: aging, neurotransmission, synapse, dauer formation, insulin pathway, C. elegans

References

  • [1].Garigan D., Hsu A., Fraser A.G., Kamath R.S., Ahringer J., Kenyon C. Genetic analysis of tissue aging in Caenorhabditis elegans: A role for heat-shock factor and bacterial proliferation. Genetics. 2002;161:1101–1112. doi: 10.1093/genetics/161.3.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [2].Kenyon C., Chang J., Gensch E., Rudner A., Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature. 1993;366:461–464. doi: 10.1038/366461a0. [DOI] [PubMed] [Google Scholar]
  • [3].Morris J.Z., Tissenbaum H.A., Ruvkun G. A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature. 1996;382:536–539. doi: 10.1038/382536a0. [DOI] [PubMed] [Google Scholar]
  • [4].Ogg S., Paradis S., Gottlieb S., Patterson G.I., Lee L., Tissenbaum H.A., et al. The Folk head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature. 1997;389:994–999. doi: 10.1038/40194. [DOI] [PubMed] [Google Scholar]
  • [5].Murphy C.T., McCarroll S.A., Bargmann C.I., Fraser A., Kamath R.S., Ahringer J., et al. Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature. 2003;424:277–283. doi: 10.1038/nature01789. [DOI] [PubMed] [Google Scholar]
  • [6].Lin K., Hsin H., Libina N., Kenyon C. Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germling signaling. Nature Genetics. 2001;28:139–145. doi: 10.1038/88850. [DOI] [PubMed] [Google Scholar]
  • [7].Tissenbaum H.A., Guarente L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature. 2001;410:227–230. doi: 10.1038/35065638. [DOI] [PubMed] [Google Scholar]
  • [8].Libina N., Berman J.R., Kenyon C. Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan. Cell. 2003;115:489–502. doi: 10.1016/S0092-8674(03)00889-4. [DOI] [PubMed] [Google Scholar]
  • [9].Ailion M., Inoue T., Weaver C.I., Holdcraft R.W., Thomas J.H. Neurosecretory control of aging in Caenorhabditis elegans. Proc Natl Acad Sci USA. 1999;96:7394–7397. doi: 10.1073/pnas.96.13.7394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [10].Berman J.R., Kenyon C. Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilichormone signaling. Cell. 2006;124:1055–1068. doi: 10.1016/j.cell.2006.01.039. [DOI] [PubMed] [Google Scholar]
  • [11].Koushika S.P., Richmond J.E., Hadwiger G., Weimer R.M., Jorgensen E.M., Nonet Ml. A post-docking role for active zone protein Rim. Nat Neurosci. 2001;4:997–1005. doi: 10.1038/nn732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [12].Madison J.M., Nurrish S., Kaplan J.M. UNC-13 interaction with syntaxin is required for synaptic transmission. Curr Biol. 2005;15:2236–2242. doi: 10.1016/j.cub.2005.10.049. [DOI] [PubMed] [Google Scholar]
  • [13].Zhen M., Jin Y. The liprin protein SYD-2 regulates the differentiation of presynaptic termini in C. elegans. Nature. 1999;401:371–375. doi: 10.1038/43886. [DOI] [PubMed] [Google Scholar]
  • [14].Nakata K., Abrams B., Grill B., Goncharov A., Huang X., Chisholm A.D., et al. Regulation of a DLK-1 and p38 MAP kinase pathway by the ubiquitin ligase RPM-1 is required for presynaptic development. Cell. 2005;120:407–420. doi: 10.1016/j.cell.2004.12.017. [DOI] [PubMed] [Google Scholar]
  • [15].Liao E.H., Hung W., Abrams B., Zhen M. An SCF-like ubiquitin ligase complex that controls presynaptic differentiation. Nature. 2004;430:345–350. doi: 10.1038/nature02647. [DOI] [PubMed] [Google Scholar]
  • [16].Nonet M.L., Saifee O., Zhao H., Rand J.B., Wei L. Synaptic transmission deficits in Caenorhabditis elegans synaptobrevin mutants. J Neurosci. 1998;18:70–80. doi: 10.1523/JNEUROSCI.18-01-00070.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [17].Jorgensen E.M., Hartwieg E., Schuske K., Nonet M.L., Jin Y., Horvitz H.R. Defective recycling of synaptic vesicles in synaptotagmin mutants of Caenorhabditis elegans. Nature. 1995;378:196–199. doi: 10.1038/378196a0. [DOI] [PubMed] [Google Scholar]
  • [18].Ogawa H., Harada S., Sassa T., Yamamoto H., Hosono R. Functional properties of the unc-64 gene encoding a Caenorhabditis elegans syntaxin. J Biol Chem. 1998;273:2192–2198. doi: 10.1074/jbc.273.4.2192. [DOI] [PubMed] [Google Scholar]
  • [19].Sassa T., Harada S., Ogawa H., Rand J.B., Maruyama I.N., Hosono R. Regulation of the UNC-18-Caenorhabditis elegans syntaxin complex by UNC-13. J Neurosci. 1999;19:4772–4777. doi: 10.1523/JNEUROSCI.19-12-04772.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [20].Weimer R.M., Richmond J.E., Davis W.S., Hadwiger G., Nonet M.L., Jorgensen E.M. Defects in synaptic vesicle docking in unc-18 mutants. Nat Neurosci. 2003;6:1023–1030. doi: 10.1038/nn1118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [21].Nam C.I., Chen L. Postsynaptic assembly induced by neurexin-neuroligin interaction and neurotransmitter. Proc Natl Acad Sci USA. 2005;102:6137–6142. doi: 10.1073/pnas.0502038102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22].Sieburth D., Ch’ng Q., Dybbs M., Tavazoie M., Kennedy S., Wang D., et al. Systematic analysis of genes required for synapse structure and function. Nature. 2005;436:510–517. doi: 10.1038/nature03809. [DOI] [PubMed] [Google Scholar]
  • [23].Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974;77:71–94. doi: 10.1093/genetics/77.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [24].Boehm M., Slack F. A developmental timing microRNA and its target regulate life span in C. elegans. Science. 2005;310:1954–1957. doi: 10.1126/science.1115596. [DOI] [PubMed] [Google Scholar]
  • [25].Inoue T., Thomas J.H. Suppressors of transforming growth factor-β pathway mutants in the Caenorhabditis elegans dauer formation pathway. Genetics. 2000;156:1035–1046. doi: 10.1093/genetics/156.3.1035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [26].Morse D.P., Bass B.L. Long RNA hairpins that contain inosine are present in Caenorhabditis elegans poly(A)+ RNA. Proc Natl Acad Sci USA. 1999;96:6048–6053. doi: 10.1073/pnas.96.11.6048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [27].Shen L.L., Wang D.Y. Differentiation and function of presynaptic active zone. Neurosci Bull. 2005;21:335–343. [Google Scholar]
  • [28].Dorman J.B., Albinder B., Shroyer T., Kenyon C. The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans. Genetics. 1995;141:1399–1406. doi: 10.1093/genetics/141.4.1399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [29].Wang D.Y., Wang Y. Screening for genetic loci affecting the active zone formation in C. elegans. Neurosci Bull. 2006;22:301–304. [PubMed] [Google Scholar]
  • [30].Sollner T., Bennett M.K., Whiteheart S.W., Scheller R.H., Rothman J.E. A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell. 1993;75:409–418. doi: 10.1016/0092-8674(93)90376-2. [DOI] [PubMed] [Google Scholar]
  • [31].Apfeld J., Kenyon C. Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature. 1999;402:804–809. doi: 10.1038/45544. [DOI] [PubMed] [Google Scholar]

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