Reid A, Sherry T J, Yücel D, Llamosas E, Nicholas H R
School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
Neuroscience. 2015 Dec 17;311:216-30. doi: 10.1016/j.neuroscience.2015.10.026. Epub 2015 Oct 19.
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末端结合蛋白（CtBPs）是转录共抑制因子，它们与多种转录因子协同作用以抑制基因表达。秀丽隐杆线虫CTBP - 1的表达已在神经系统和皮下组织中被观察到。在秀丽隐杆线虫中，CTBP - 1调节多个过程，包括对乙醇的急性功能耐受性，并且在神经系统中发挥作用，调节寿命以及一个名为lips - 7的脂肪酶基因的表达。神经系统结构和/或功能异常可导致行为改变。在此，我们证明ctbp - 1突变体的探索行为减少。我们对参与调节运动的一部分神经元进行检查发现，在第四幼虫（L4）阶段，ctbp - 1突变体中背侧SMD（SMDD）神经元的轴突形态发生改变。在L4阶段，在内源性ctbp - 1启动子的控制下表达CTBP - 1可挽救ctbp - 1突变体的探索行为表型和SMDD轴突结构缺陷。有趣的是，在ctbp - 1突变体中，突触前标记RAB - 3定位于SMDD轴突的错位部分。对成年期第1、3和5天的SMDD轴突形态进行进一步分析发现，显示SMDD轴突形态缺陷的ctbp - 1突变体数量在成年早期增加，并且观察到的缺陷在性质上似乎更严重。CTBP - 1在神经系统中显著表达，在皮下组织中检测到弱表达。令人惊讶的是，仅在神经系统或皮下组织中表达CTBP - 1a并不能恢复ctbp - 1突变体中正确的SMDD轴突结构。我们的结果证明了CTBP - 1在秀丽隐杆线虫的探索行为和SMDD轴突形态调节中的作用。
