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dc.contributor.author
Broughton, Susan
dc.contributor.author
Alic, Nazif
dc.contributor.author
Slack, Cathy
dc.contributor.author
Bass, Timothy
dc.contributor.author
Ikeya, Tomoatsu
dc.contributor.author
Vinti, Giovanna
dc.contributor.author
Tommasi, Anna Maria
dc.contributor.author
Driege, Yasmine
dc.contributor.author
Hafen, Ernst
dc.contributor.author
Partridge, Linda
dc.date.accessioned
2018-08-09T12:48:34Z
dc.date.available
2017-06-08T21:08:07Z
dc.date.available
2018-08-09T12:48:34Z
dc.date.issued
2008-11-13
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0003721
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/13726
dc.identifier.doi
10.3929/ethz-b-000013726
dc.description.abstract
The insulin/IGF-like signalling (IIS) pathway has diverse functions in all multicellular organisms, including determination of lifespan. The seven insulin-like peptides (DILPs) in Drosophila are expressed in a stage- and tissue-specific manner. Partial ablation of the median neurosecretory cells (mNSCs) in the brain, which produce three DILPs, extends lifespan, reduces fecundity, alters lipid and carbohydrate metabolism and increases oxidative stress resistance. To determine if reduced expression of DILPs is causal in these effects, and to investigate possible functional diversification and redundancy between DILPs, we used RNA interference to lower specifically the transcript and protein levels of dilp2, the most highly expressed of the mNSC-derived DILPs. We found that DILP2 was limiting only for the increased whole-body trehalose content associated with mNSC-ablation. We observed a compensatory increase in dilp3 and 5 mRNA upon dilp2 knock down. By manipulation of dfoxo and dInR, we showed that the increase in dilp3 is regulated via autocrine insulin signaling in the mNSCs. Our study demonstrates that, despite the correlation between reduced dilp2 mRNA levels and lifespan-extension often observed, DILP2 reduction is not sufficient to extend lifespan. Nor is the increased trehalose storage associated with reduced IIS sufficient to extend lifespan. To understand the normal regulation of expression of the dilps and any functional diversification between them will require independent control of the expression of different dilps.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Public Library of Science
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.title
Reduction of DILP2 in Drosophila triages a metabolic phenotype from lifespan revealing redundancy and compensation among DILPs
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
ethz.journal.title
PLoS ONE
ethz.journal.volume
3
en_US
ethz.journal.issue
11
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e3721
en_US
ethz.size
9 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.publication.place
[s.l.]
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03710 - Hafen, Ernst / Hafen, Ernst
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03710 - Hafen, Ernst / Hafen, Ernst
ethz.date.deposited
2017-06-08T21:08:27Z
ethz.source
ECIT
ethz.identifier.importid
imp59364c307fe0142728
ethz.ecitpid
pub:25209
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-12T17:42:05Z
ethz.rosetta.lastUpdated
2018-11-07T23:15:10Z
ethz.rosetta.versionExported
true
ethz.COinS
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