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Gene Regulation and Epigenetics

開催日 2014/9/13
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Differential expression and dendritic function of SRF coactivator MKL2 isoforms in cortical neurons

  • P3-035
  • 田渕 明子 / Akiko Tabuchi:1 石橋 悠太 / Yuta Ishibashi:1 庄司 しずく / Shizuku Shoji:1 久保 友喜美 / Yukimi Kubo:1 袴田 知之 / Tomoyuki Hakamata:1 宮田 智陽 / Tomoaki Miyata:1 佐藤 夏美 / Natsumi Satoh:1 阪上 洋行 / Hiroyuki Sakagami:2 福地 守 / Mamoru Fukuchi:1 津田 正明 / Masaaki Tsuda:1 
  • 1:富山大院・医薬・分子神経生物 / Laboratory of Molecular Neurobiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama Japan 2:北里大・医・解剖 / Department of Anatomy, Kitasato University, School of Medicine, Kanagawa, Japan 

Serum response factor (SRF) transcriptional coactivators, megakaryoblastic leukemia family members, consist of MKL1 and MKL2. MKL1 and MKL2 are highly expressed in the brain and are suggested to modulate neuronal morphology. Previously, we identified MKL1 isoforms including a novel one and found that they are expressed differently in the developing brain. In this study, we have characterized that MKL2 isoforms including a novel MKL2 isoform named spliced neuronal long isoform of SRF transcriptional coactivator (SOLOIST). In the nucleotide sequence and deduced domain structure of SOLOIST, there is only one exon-difference between SOLOIST and isoform 3: alternative splicing gives rise to the exon codes for 21 amino acid residues. SOLOIST and isoform 1 are enriched in the brain and neurons and are up-regulated during brain development. Conversely, isoform 3 is detected in a variety of tissues examined, expressed in both neurons and astrocytes and down-regulated in the developing brain. The expression of isoform 2 in the brain turned out to be very faint and undetectable by qPCR. In the comparable expressional analyses of these MKL2 isoforms, isoform 1 is the most abundant (approximately seventy percent), the expression of SOLOIST is less than twenty percent and that of isoform 3 is around ten percent of total MKL2 content in the brain. Overexpression study revealed that the SRF coactivator function of isoforms 1, 3 and SOLOIST are observed in cortical neurons. However, their effects on dendritic complexity were different. That is, the overexpression of isoform 1 in cortical neurons increased the dendritic complexity, whereas that of SOLOIST decreased it. Taken together, these findings suggest that MKL2 isoforms, which are differentially expressed in the developing brain, may play reciprocal roles in dendritic morphology, possibly contributing to fine-tuning neuronal function.

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