THE C-TERMINAL BINDING PROTEIN (CTBP-1) REGULATES DORSAL SMD AXONAL MORPHOLOGY IN CAENORHABDITIS ELEGANS


Reid A., Sherry T. J., Yuecel D., Llamosas E., Nicholas H. R.

NEUROSCIENCE, cilt.311, ss.216-230, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 311
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1016/j.neuroscience.2015.10.026
  • Dergi Adı: NEUROSCIENCE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.216-230
  • Anahtar Kelimeler: Caenorhabditis elegans, CTBP-1, exploration behavior, SMD, axonal morphology, NERVOUS-SYSTEM, CELLULAR PHOSPHOPROTEIN, TRANSCRIPTION FACTOR, NEGATIVE MODULATION, THAP DOMAIN, GUIDANCE, BOMBARDMENT, NAVIGATION, OUTGROWTH, CIRCUIT
  • Erciyes Üniversitesi Adresli: Evet

Özet

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. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.