当前位置: X-MOL 学术J. Neurochem. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Expression of SOLOIST/MRTFB i4, a novel neuronal isoform of the mouse serum response factor coactivator myocardin-related transcription factor-B, negatively regulates dendritic complexity in cortical neurons
Journal of Neurochemistry ( IF 4.7 ) Pub Date : 2020-07-08 , DOI: 10.1111/jnc.15122
Yuta Ishibashi 1 , Shizuku Shoji 1 , Daisuke Ihara 1, 2 , Yukimi Kubo 1 , Takuro Tanaka 1 , Hiroki Tanabe 1 , Tomoyuki Hakamata 1 , Tomoaki Miyata 1 , Natsumi Satou 1 , Hiroyuki Sakagami 3 , Mineyuki Mizuguchi 4 , Keietsu Kikuchi 1 , Mamoru Fukuchi 1, 5 , Masaaki Tsuda 1 , Ichiro Takasaki 6 , Akiko Tabuchi 1, 2
Affiliation  

Megakaryoblastic leukemia 2 (MKL2)/myocardin-related transcription factor-B (MRTFB), a serum response factor (SRF) coactivator, is an important regulator of gene expression and neuronal morphology. Here, we show that different mouse MRTFB splice isoforms, including a novel fourth MRTFB isoform named spliced neuronal long isoform of SRF transcriptional coactivator (SOLOIST)/MRTFB isoform 4 (MRTFB i4), play distinct roles in this process. SOLOIST/MRTFB i4 has a short exon that encodes 21 amino acid residues ahead of the first RPXXXEL (RPEL) motif in MRTFB isoform 3. Quantitative PCR revealed that SOLOIST/MRTFB i4 and isoform 1 were enriched in the forebrain and neurons, and up-regulated during brain development. Conversely, isoform 3 was detected in various tissues, including both neurons and astrocytes, and was down-regulated in the developing brain. Reporter assays supported the SRF-coactivator function of SOLOIST/MRTFB i4 as well as isoform 1. Acute expression of MRTFB isoform 1, but not isoform 3 or SOLOIST/MRTFB i4, in neuronal cells within 24 hr drastically increased endogenous immediate early gene [c-fos, egr1, and activity-regulated cytoskeleton-associated protein] expression, but not endogenous actinin α1, β-actin, gelsolin, or srf gene expression measured by qPCR. Over-expression of SOLOIST/MRTFB i4 reduced the dendritic complexity of cortical neurons, whereas over-expression of isoform 1 increased this complexity. Co-expression of isoform 1 and SOLOIST/MRTFB i4 in cortical neurons revealed that isoform 1 competitively counteracted down-regulation by SOLOIST/MRTFB i4. Our findings indicate that MRTFB isoforms have unique expression patterns and differential effects on gene expression and dendritic complexity, which contribute to shaping neuronal circuits, at least in part.

中文翻译:

SOLOIST/MRTFB i4 的表达,小鼠血清反应因子共激活因子心肌素相关转录因子 B 的新型神经元异构体,负调节皮质神经元的树突复杂性

巨核细胞白血病 2 (MKL2)/心肌素相关转录因子-B (MRTFB) 是一种血清反应因子 (SRF) 共激活因子,是基因表达和神经元形态的重要调节因子。在这里,我们展示了不同的小鼠 MRTFB 剪接异构体,包括一种新的第四种 MRTFB 异构体,称为 SRF 转录共激活因子 (SOLOIST)/MRTFB 异构体 4 (MRTFB i4) 的拼接神经元长异构体,在此过程中发挥着不同的作用。SOLOIST/MRTFB i4有一个短外显子,在 MRTFB 异构体 3 中的第一个 RPXXXEL (RPEL) 基序之前编码 21 个氨基酸残基。定量 PCR 显示SOLOIST/MRTFBi4 和亚型 1 在前脑和神经元中富集,并在大脑发育过程中上调。相反,在包括神经元和星形胶质细胞在内的各种组织中检测到同种型 3,并且在发育中的大脑中被下调。报告基因分析支持 SOLOIST/MRTFB i4 和亚型 1 的 SRF 共激活功能。MRTFB 亚型 1 的急性表达,但不是亚型 3 或 SOLOIST/MRTFB i4,在 24 小时内的神经元细胞中急剧增加内源性即刻早期基因 [c - fosegr 1 和活性调节的细胞骨架相关蛋白] 表达,但不包括内源性肌动蛋白 α1β-肌动蛋白凝溶胶蛋白srf通过 qPCR 测量的基因表达。SOLOIST/MRTFB i4 的过度表达降低了皮质神经元的树突复杂性,而异构体 1 的过度表达增加了这种复杂性。同种型 1 和 SOLOIST/MRTFB i4 在皮质神经元中的共表达表明同种型 1 竞争性地抵消了 SOLOIST/MRTFB i4 的下调。我们的研究结果表明,MRTFB 亚型具有独特的表达模式和对基因表达和树突复杂性的不同影响,这至少部分有助于塑造神经元回路。
更新日期:2020-07-08
down
wechat
bug