Functional characterization of the adenylyl cyclase gene sgs-1 by analysis of a mutational spectrum in Caenorhabditis elegans.
The sgs-1 (suppressor of activated Galpha(s)) gene encodes one of the four adenylyl cyclases in the nematode C. elegans and is most similar to mammalian adenylyl cyclase type IX. We isolated a complete loss-of-function mutation in sgs-1 and found it to result in animals with retarded development that arrest in variable larval stages. sgs-1 mutant animals exhibit lethargic movement and pharyngeal pumping and (while not reaching adulthood) have a mean life span that is > 50% extended compared to wild type. An extensive set of reduction-of-function mutations in sgs-1 was isolated in a screen for suppressors of a neuronal degeneration phenotype induced by the expression of a constitutively active version of the heterotrimeric Galpha(s) subunit of C. elegans. Although most of these mutations change conserved residues within the catalytic domains of sgs-1, mutations in the less-conserved transmembrane domains are also found. The sgs-1 reduction-of-function mutants are viable and have reduced locomotion rates, but do not show defects in pharyngeal pumping or life span.
Moorman
Celine
C
Hubrecht Laboratory, Centre for Biomedical Genetics, 3584 CT, Utrecht, The Netherlands.
Plasterk
Ronald H A
RH
D000262:Adenylyl Cyclases / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002384:Catalysis; D004252:DNA Mutational Analysis; D019204:GTP-Binding Proteins / Q000378:metabolism; D020043:Genes, Essential; D017238:Genes, Helminth; D008124:Locomotion / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D017434:Protein Structure, Tertiary
D029742:Caenorhabditis elegans Proteins; D019204:GTP-Binding Proteins; C469573:ACY-1 protein, C elegans; D000262:Adenylyl Cyclases