title: The C-terminal binding protein (CTBP-1) regulates dorsal SMD axonal morphology in Caenorhabditis elegans.
abstract: C-terminal binding proteins (CtBPs) are transcriptional co-repressors which cooperate with a variety of transcription factors to repress gene expression. Caenorhabditis elegans CTBP-1 expression has been observed in the nervous system and hypodermis. In C. elegans, CTBP-1 regulates several processes including Acute Functional Tolerance to ethanol and functions in the nervous system to modulate both lifespan and expression of a lipase gene called lips-7. Incorrect structure and/or function of the nervous system can lead to behavioral changes. Here, we demonstrate reduced exploration behavior in ctbp-1 mutants. Our examination of a subset of neurons involved in regulating locomotion revealed that the axonal morphology of dorsal SMD (SMDD) neurons is altered in ctbp-1 mutants at the fourth larval (L4) stage. Expressing CTBP-1 under the control of the endogenous ctbp-1 promoter rescued both the exploration behavior phenotype and defective SMDD axon structure in ctbp-1 mutants at the L4 stage. Interestingly, the pre-synaptic marker RAB-3 was found to localize to the mispositioned portion of SMDD axons in a ctbp-1 mutant. Further analysis of SMDD axonal morphology at days 1, 3 and 5 of adulthood revealed that the number of ctbp-1 mutants showing an SMDD axonal morphology defect increases in early adulthood and the observed defect appears to be qualitatively more severe. CTBP-1 is prominently expressed in the nervous system with weak expression detected in the hypodermis. Surprisingly, solely expressing CTBP-1a in the nervous system or hypodermis did not restore correct SMDD axonal structure in a ctbp-1 mutant. Our results demonstrate a role for CTBP-1 in exploration behavior and the regulation of SMDD axonal morphology in C. elegans.
authors.affiliation: School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Reid
authors.affiliation: School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: T J
authors.initials: TJ
authors.lastname: Sherry
authors.affiliation: School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Yücel
authors.affiliation: School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Llamosas
authors.affiliation: School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: hannah.nicholas@sydney.edu.au.
authors.forename: H R
authors.initials: HR
authors.lastname: Nicholas
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology; D008856:Microscopy, Fluorescence; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism
chemical_list: C525550:CTBP-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D012097:Repressor Proteins; D020692:rab3 GTP-Binding Proteins
keywords: CTBP-1; Caenorhabditis elegans; SMD; axonal morphology; exploration behavior