G protein hyperactivation of the Caenorhabditis elegans adenylyl cyclase SGS-1 induces neuronal degeneration

EMBO J. 1998 Sep 1;17(17):5059-65. doi: 10.1093/emboj/17.17.5059.


Expression of a constitutively activated version of the heterotrimeric G protein alpha-subunit Galphas results in the swelling and vacuolization of a specific subset of ventral nerve cord motoneurons of Caenorhabditis elegans. A second site modifier (sgs-1) that completely suppresses this neuronal degeneration has been isolated. sgs-1 was cloned and was shown to encode an adenylyl cyclase which is most similar to mammalian adenylyl cyclase type IX. Mutations in sgs-1 change residues that are conserved among different adenylyl cyclases. These mutations are located in the two catalytic domains and in the first multiple transmembrane spanning region of the predicted protein. An sgs-1 reporter construct shows a general neuronal expression pattern, demonstrating that sgs-1 is expressed in the neurons that are susceptible to activated Galphas-induced cell death. A second C.elegans adenylyl cyclase gene (acy-2) was analyzed as well. In contrast to sgs-1, acy-2 shows a restricted expression pattern and loss of acy-2 function results in early larval lethality. These results suggest that SGS-1 is a target of Galphas signaling in motoneurons, whereas an interaction of Galphas with ACY-2, probably in the canal-associated neurons, is required for viability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / genetics
  • Adenylyl Cyclases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / physiology*
  • Cell Death / genetics
  • Cloning, Molecular
  • GTP-Binding Protein alpha Subunits, Gs / metabolism*
  • Molecular Sequence Data
  • Motor Neurons / pathology*
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nervous System / pathology*
  • Sequence Analysis, DNA
  • Suppression, Genetic
  • Tissue Distribution


  • Nerve Tissue Proteins
  • GTP-Binding Protein alpha Subunits, Gs
  • Adenylyl Cyclases

Associated data

  • GENBANK/AF022968