title: Central and C-terminal domains of heterotrimeric G protein gamma subunits differentially influence the signaling necessary for primordial germ cell migration.
abstract: Heterotrimeric G protein signaling is involved in many pathways essential to development including those controlling cell migration, proliferation, differentiation and apoptosis. One key developmental event known to rely on proper heterotrimeric G protein signaling is primordial germ cell (PGC) migration. We previously developed an in vivo PGC migration assay that identified differences in the signaling capacity of G protein gamma subunits. In this study we developed Gγ subunit chimeras to determine the regions of Gγ isoforms that are responsible for these differences. The central section of the Gγ subunit was found to be necessary for the ability of a Gγ subunit to mediate signaling involved in PGC migration. Residues found in the carboxy-terminal segment of Gγ transducin (gngt1) were found to be responsible for the ability of this subunit to disrupt PGC migration. The type of prenylation did not affect the ability of a Gγ subunit to reverse prenylation-deficient-Gγ-induced PGC migration defects. However, a version of gng2, engineered to be farnesylated instead of geranylgeranylated, still lacks the ability to reverse PGC migration defects known to result from treatment of zebrafish with geranylgeranyl transferase inhibitors (GGTI), supporting the notion that Gγ subunits are one of several protein targets that need to be geranylgeranylated to orchestrate the proper long-range migration of PGCs.
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Mulligan
authors.forename: Steven A
authors.initials: SA
authors.lastname: Farber
mesh_terms: D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002465:Cell Movement; D003001:Cloning, Molecular; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors; D005854:Germ Cells / Q000378:metabolism / Q000502:physiology*; D047468:Immunoprecipitation; D007814:Larva / Q000235:genetics / Q000378:metabolism; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000378:metabolism; D017368:Protein Prenylation; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D014166:Transferases / Q000037:antagonists & inhibitors; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D062366:para-Aminobenzoates
chemical_list: C568354:GGTI 2166; D044388:GTP-Binding Protein gamma Subunits; C521434:GngT1 protein, zebrafish; D020033:Protein Isoforms; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D029961:Zebrafish Proteins; D062366:para-Aminobenzoates; D014166:Transferases; D007930:Leucine; D010129:4-Aminobenzoic Acid