ogt-1;sgk-1

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Genetic mutants with ogt-1, sgk-1 alterations

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

Temperature °C
20
Diet
NGM; OP50
Lifespan (days)
16.6
Lifespan change (compared to wild type)
4.40%
Phenotype
Lifespan of sgk-1(ok538) mutants is dependent on protein O-GlcNAc modification as seen in sgk-1; ogt-1 (B) double mutants.
Lifespan comparisons
Double mutant ogt-1(ok1474);sgk-1(ok538) has a lifespan of 16.6 days, while single mutant sgk-1(ok538) has a lifespan of 29.8 days, single mutant ogt-1(ok1474) has a lifespan of 12.9 days and wild type has a lifespan of 15.9 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Rahman MM et al., 2010, Intracellular protein glycosylation modulates insulin mediated lifespan in C.elegans. Aging (Albany NY). 2(10):678-90 20952811 Click here to select all mutants from this PubMed ID in the graph
Abstract
O-linked-β-N-acetylglucosamine (O-GlcNAc) modification is a regulatory, nuclear and cytoplasmic post-translational glycosylation of proteins associated with age-related diseases such as Alzheimer's, Parkinson's, and type II diabetes. Global elevation of O-GlcNAc levels on intracellular proteins can induce insulin resistance, the hallmark of type II diabetes, in mammalian systems. InC. elegans, attenuation of the insulin-like signal transduction pathway increases adult lifespan of the nematode. We demonstrate that the O-GlcNAc cycling enzymes OGT and OGA, which add and remove O-GlcNAc respectively, modulate lifespan in C. elegans. Median adult lifespan is increased in an oga-1 deletion strain while median adult life span is decreased upon ogt-1 deletion. The O-GlcNAc-mediated effect on nematode lifespan is dependent on the FoxO transcription factor DAF-16. DAF-16 is a key factor in the insulin-like signal transduction pathway to regulate reproductive development, lifespan, stress tolerance, and dauer formation in C. elegans. Our data indicates that O-GlcNAc cycling selectively influences only a subset of DAF-16 mediated phenotypes, including lifespan and oxidative stress resistance. We performed an affinity purification of O-GlcNAc-modified proteins and observed that a high percentage of these proteins are regulated by insulin signaling and/or impact insulin pathway functional outcomes, suggesting that the O-GlcNAc modification may control downstream effectors to modulate insulin pathway mediated cellular processes.

Search genes: ogt-1 sgk-1

Entrez ID
Symbol
GenAge
Wormbase ID

176000
ogt-1
View on GenAge (ogt-1)
WBGene00003858

O-linked GlcNAc Transferase;UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase

Locus: CELE_K04G7.3

Wormbase description: ogt-1 encodes an ortholog of O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT; OMIM:300255) with 12 N-terminal tetratricopeptide (TPR) domains (generally thought to enable protein-protein interactions) and a C-terminal putative catalytic domain; although loss of ogt-1 activity has no effect on overall viability or fertility, ogt-1 mutations result in alterations in macronutrient storage and can suppress constitutive dauer formation in daf-2 mutants suggesting that, in C. elegans, ogt-1 may play a regulatory role in nutrient sensing and insulin-like signaling pathways; OGT-1 is expressed in embryos, where it exhibits nuclear and punctate perinuclear localization.

Entrez ID
Symbol
GenAge
Wormbase ID

181697
sgk-1
View on GenAge (sgk-1)
WBGene00004789

Serine/threonine-protein kinase sgk-1

Locus: CELE_W10G6.2

Wormbase description: sgk-1 encodes a serine/threonine protein kinase that is orthologous to the mammalian serum- and glucocorticoid-inducible kinases (SGKs); in C. elegans, sgk-1 activity is required for normal egg laying, generation time, stress response, and adult life span; SGK-1 forms a complex with the AKT kinases with which it functions in parallel to mediate certain aspects of DAF-2/insulin-signaling; SGK-1 phosphorylates DAF-16 in vitro in a manner strictly dependent upon pdk-1 which encodes a 3-phosphoinositide-dependent kinase; an SGK-1::GFP fusion protein is expressed beginning in late embryonic stages and in larvae is seen in sensory and motor neurons as well as in the intestine; in neurons SGK-1::GFP localizes to the cytoplasm and the nucleus, while in the intestine SGK-1::GFP is found exclusively in the cytoplasm.

Orthologs of ogt-1;sgk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Ogt;Sgk3
Mus musculus	Ogt;Sgk2
Mus musculus	Ogt;Sgk1

Orthologs of ogt-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	sxc
Mus musculus	Ogt

Orthologs of sgk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Sgk3
Mus musculus	Sgk2
Mus musculus	Sgk1