Psychiatry related information on goa-1

• Mutations in goa-1, dgk-1, eat-16, or eat-11 strongly or completely suppressed unc-43(gf) lethargy, but affected other mutants with reduced locomotion only weakly [1].

High impact information on goa-1

• The goa-1 gene encoding the alpha subunit of the heterotrimeric guanosine triphosphate-binding protein (G protein) Go from Caenorhabditis elegans is expressed in most neurons, and in the muscles involved in egg laying and male mating [2].
• Mutations in the goa-1 gene, which encodes an alpha subunit of Go (G alpha o), cause behavioral defects similar to those observed in mutants that lack the neurotransmitter serotonin (5-HT), and goa-1 mutants are partially resistant to exogenous 5-HT [3].
• Animals defective in either gene display a hyperactive phenotype similar to that of goa-1 loss-of-function mutants [4].
• Mutants lacking goa-1 G(alpha)0 accumulated abnormally high levels of the DAG-binding protein UNC-13 at motor neuron nerve terminals, suggesting that serotonin inhibits synaptic transmission by decreasing the abundance of UNC-13 at release sites [5].
• RIC-8 was genetically shown to act in concert with goa-1 to regulate centrosome movements in C. elegans . Interestingly, mammalian RIC-8 was recently found to behave as a GEF for Galpha subunits in vitro . We show that reduction of function of ric-8 results in a 1 cell embryo phenotype very similar to the phenotype of embryos depleted of Galpha [6].

Biological context of goa-1

• In ric-8 reduction of function backgrounds, the embryonic lethality, spindle misalignments and delayed nuclear migration are strongly enhanced by a 50% reduction in maternal goa-1 gene dosage [7].
• The system allows comparison of distinct genotypes that affect movement similarly (activation of Gq-alpha versus loss of Go-alpha function), as well as of different mutant alleles at a single locus (null and dominant negative alleles of the goa-1 gene, which encodes Go-alpha) [8].

Anatomical context of goa-1

• Through Nomarski analysis we show that goa-1 and ric-8 mutant embryos exhibit defects in multiple events that involve centrosomes, including one-cell posterior centrosome rocking, P(1) centrosome flattening, mitotic spindle alignment, and nuclear migration [7].

Associations of goa-1 with chemical compounds

• Loss-of-function mutants of the gene goa-1, which codes for the alpha-subunit of Go, have EC(50)s for the VA isoflurane of 1.7- to 2.4-fold that of wild type [9].
• The RGS overexpressing strains, a goa-1 missense mutant found to carry a novel mutation near the GTP-binding domain, and eat-16(rf) mutants, which suppress goa-1(gf) mutations, are all halothane resistant; goa-1(null) mutants have wild-type sensitivities [9].

Other interactions of goa-1

• Interestingly, these characteristic defects resembled phenotypes observed in gain-of-function mutants of unc-43/Ca(2+)-calmodulin-dependent protein kinase II (CaMKII) and goa-1/G(o)-protein alpha-subunit [10].
• Strains overexpressing egl-10, which codes for an RGS protein negatively regulating goa-1, are also isoflurane resistant [9].

References