oga-1;sgk-1

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Genetic mutants with oga-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)
26.2
Lifespan change (compared to wild type)
64.78%
Phenotype
The adult lifespan extension associated with the oga-1(ok1207) mutant is not synergistic or additive with mutations of the long-lived insulin signaling pathway kinase sgk-1.
Lifespan comparisons
Double mutant oga-1(ok1207);sgk-1(ok538) has a lifespan of 26.2 days, while single mutant sgk-1(ok538) has a lifespan of 29.8 days, single mutant oga-1(ok1207) has a lifespan of 20.9 days and wild type has a lifespan of 15.9 days.
Type of interaction
See methods
Dependent
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: oga-1 sgk-1

Entrez ID
Symbol
GenAge
Wormbase ID

181164
oga-1
View on GenAge (oga-1)
WBGene00020596

O-GlcNAc selective N-Acetyl-beta-D-glucosaminidase (O-GlcNAcase)

Locus: CELE_T20B5.3

Wormbase description: oga-1 encodes an ortholog of mammalian O-linked N-acetylglucosamine (O-GlcNAc)-selective N-acetyl-beta-D-glucosaminidase (O-GlcNAcase); a polymorphism of OGA-1's human ortholog MGEA5 is associated with type 2 diabetes, and OGA-1 appears to be required for fine-tuning of insulin signalling; oga-1(ok1207) mutants are viable and fertile but accumulate O-GlcNAc on nuclear pores and other proteins, while showing S/T-phosphorylation of proteins, increased GSK-3beta activity, excess glycogen and trehalose, and decreased lipid storage; oga-1(ok1207) mutations enhance the Daf-c phenotype of daf-2(e1370ts) alleles even under conditions where oga-1(ok1207) alone diminishes dauer formation.

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 oga-1;sgk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Mgea5;Sgk3
Mus musculus	Mgea5;Sgk2
Mus musculus	Mgea5;Sgk1

Orthologs of oga-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Oga
Mus musculus	Mgea5

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