glp-1;kri-1

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Genetic mutants with glp-1, kri-1 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
20
Lifespan (days)
17.0
Lifespan comparisons
Double mutant glp-1(e2141ts);kri-1(ok1251) has a lifespan of 17.0 days, while single mutant glp-1(e2141ts) has a lifespan of 30.9 days.
Citation
View abstract
Berman JR, Kenyon C, 2006, Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling. Cell. 124(5):1055-68 16530050 Click here to select all mutants from this PubMed ID in the graph
Abstract
In C. elegans, removing the germ cells extends life span by triggering the nuclear localization and activation of the DAF-16/FOXO transcription factor in the intestine. In this study, we identify and analyze genes required for germline removal to extend life span. We find that the reproductive system communicates with the intestine through lipophilic-hormone signaling and that a gene called kri-1 is likely to act in the intestine to promote DAF-16 nuclear localization in response to this signal. This lipophilic-signaling pathway and kri-1 are not required for DAF-16's nuclear localization and life-span extension in animals with decreased insulin/IGF-1 signaling. Thus, this pathway specifically enables the integration of cues from the reproductive system with central DAF-16-activation pathways to influence the aging of the animal.

Temperature °C
20
Lifespan (days)
17.6
Lifespan comparisons
Double mutant glp-1(e2141ts);kri-1(ok1251) has a lifespan of 17.6 days, while single mutant glp-1(e2141ts) has a lifespan of 27.7 days.
Citation
View abstract
Berman JR, Kenyon C, 2006, Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling. Cell. 124(5):1055-68 16530050 Click here to select all mutants from this PubMed ID in the graph
Abstract
In C. elegans, removing the germ cells extends life span by triggering the nuclear localization and activation of the DAF-16/FOXO transcription factor in the intestine. In this study, we identify and analyze genes required for germline removal to extend life span. We find that the reproductive system communicates with the intestine through lipophilic-hormone signaling and that a gene called kri-1 is likely to act in the intestine to promote DAF-16 nuclear localization in response to this signal. This lipophilic-signaling pathway and kri-1 are not required for DAF-16's nuclear localization and life-span extension in animals with decreased insulin/IGF-1 signaling. Thus, this pathway specifically enables the integration of cues from the reproductive system with central DAF-16-activation pathways to influence the aging of the animal.

Search genes: glp-1 kri-1

Entrez ID
Symbol
GenAge
Wormbase ID

176286
glp-1
View on GenAge (glp-1)
WBGene00001609

Protein glp-1

Locus: CELE_F02A9.6

Wormbase description: glp-1 encodes an N-glycosylated transmembrane protein that, along with LIN-12, comprises one of two C. elegans members of the LIN-12/Notch family of receptors; from the N- to the C-terminus, GLP-1 is characterized by ten extracellular EGF-like repeats, three LIN-12/Notch repeats, a CC-linker, a transmembrane domain, a RAM domain, six intracellular ankyrin repeats, and a PEST sequence; in C. elegans, GLP-1 activity is required for cell fate specification in germline and somatic tissues; in the germline, GLP-1, acting as a receptor for the DSL family ligand LAG-2, is essential for mitotic proliferation of germ cells and maintenance of germline stem cells; in somatic tissues, maternally provided GLP-1, acting as a receptor for the DSL family ligand APX-1, is required for inductive interactions that specify the fates of certain embryonic blastomeres; GLP-1 is also required for some later embryonic cell fate decisions, and in these decisions its activity is functionally redundant with that of LIN-12; GLP-1 expression is regulated temporally and spatially via translational control, as GLP-1 mRNA, present ubiquitously in the germline and embryo, yields detectable protein solely in lateral, interior, and endomembranes of distal, mitotic germ cells, and then predominantly in the AB blastomere and its descendants in the early embryo; proper spatial translation of glp-1 mRNA in the embryo is dependent upon genes such as the par genes, that are required for normal anterior-posterior asymmetry in the early embryo; signaling through GLP-1 controls the activity of the downstream Notch pathway components LAG-3 and LAG-1, the latter being predicted to function as part of a transcriptional feedback mechanism that positively regulates GLP-1 expression; signaling through the DNA-binding protein LAG-1 is believed to involve a direct interaction between LAG-1 and the GLP-1 RAM and ankyrin domains

Entrez ID
Symbol
GenAge
Wormbase ID

191275
kri-1
View on GenAge (kri-1)
WBGene00013955

human KRIT 1 (Krev interaction trapped/cerebral cavernous malformation 1) homolog

Locus: CELE_ZK265.1

Wormbase description: kri-1 encodes an ankyrin repeat and FERM domain-containing protein orthologous to human KRIT1 (Krev interaction trapped/cerebral cavernous malformation 1, OMIM:604214); kri-1 was identified in RNAi screens for genes required for DAF-16-dependent lifespan extension in germline-depleted animals; subsequent analysis of kri-1 mutations suggests that KRI-1 is required for proper localization of DAF-16 in the intestine in response to germline loss; a rescuing KRI-1::GFP construct is expressed in larval and adult stages in pharyngeal and intestinal cells; the KRI-1::GFP is generally diffuse, but also localizes to apical and apicolateral cell surfaces as well as to intestinal nuclei in some animals.

Orthologs of glp-1;kri-1 in SynergyAge

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Species	Gene

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Species	Gene

Orthologs of glp-1 in SynergyAge

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Species	Gene

Orthologs of kri-1 in SynergyAge

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Species	Gene

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Species	Gene
Mus musculus	Krit1