Smooth muscle caldesmon modulates peristalsis in the wild type and non-innervated zebrafish intestine.
Smooth muscle caldesmon modulates peristalsis in the wild type and non-innervated zebrafish intestine.
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DOI：
10.1111/j.1365-2982.2011.01844.x
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发表时间：
2012-03
影响因子：
3.5
通讯作者：
Pack M
中科院分区：
文献类型：
--
作者：
Abrams J;Davuluri G;Seiler C;Pack M
肌动蛋白结合蛋白Caldesmon（h-CaD）的高分子量同种型通过调节肌球蛋白头的跨桥循环来调节平滑肌收缩功能。h-CaD的正常抑制活性受肠神经系统的调节;然而，h-CaD在肠痉挛期间的作用从未被研究过。我们确定了一个人CALD 1基因编码的h-CaD异构体在肠道平滑肌中表达的斑马鱼paradigm。我们研究的作用，h-CaD在斑马鱼幼虫肠道pathogenesis通过敲低h-CaD蛋白使用反义morpholino寡核苷酸。我们还开发了转基因斑马鱼，表达来自h-CaD肌球蛋白和肌动蛋白结合结构域的抑制肽，并研究其对野生型斑马鱼幼虫和缺乏肠神经的sox 10无色突变体幼虫的生长的影响。基因组分析确定了两个斑马鱼Caldesmon旁系同源。cald 1a的直系同源物编码的高分子量的异构体产生的选择性剪接，其肠道表达仅限于平滑肌。通过h-CaD敲低和编码抑制性肌球蛋白和肌动蛋白结合结构域肽的转基因表达，野生型斑马鱼幼虫的推进性肠蠕动增加。蠕动在非神经支配的肠sox 10无色幼虫部分恢复h-CaD敲低和肌球蛋白结合肽的表达。干扰正常的抑制功能的h-钙调素增强肠pronosis在野生型斑马鱼幼虫和突变体幼虫，缺乏肠神经，从而证实了调节平滑肌收缩的肌动蛋白丝的生理作用。
The high molecular weight isoform of the actin-binding protein Caldesmon (h-CaD) regulates smooth muscle contractile function by modulating cross-bridge cycling of myosin heads. The normal inhibitory activity of h-CaD is regulated by the enteric nervous system; however, the role of h-CaD during intestinal peristalsis has never been studied. We identified a zebrafish paralog of the human CALD1 gene that encodes an h-CaD isoform expressed in intestinal smooth muscle. We examined the role of h-CaD during intestinal peristalsis in zebrafish larvae by knocking down the h-CaD protein using an antisense morpholino oligonucleotide. We also developed transgenic zebrafish that express inhibitory peptides derived from the h-CaD myosin and actin-binding domains, and examined their effect on peristalsis in wild-type zebrafish larvae and sox10colourless mutant larvae that lack enteric nerves. Genomic analyses identified two zebrafish Caldesmon paralogs. The cald1a ortholog encoded a high molecular weight isoform generated by alternative splicing whose intestinal expression was restricted to smooth muscle. Propulsive intestinal peristalsis was increased in wild-type zebrafish larvae by h-CaD knockdown and by expression of transgenes encoding inhibitory myosin and actin-binding domain peptides. Peristalsis in the non-innervated intestine of sox10colourless larvae was partially restored by h-CaD knockdown and expression of the myosin-binding peptide. Disruption of the normal inhibitory function of h-CaD enhances intestinal peristalsis in both wild-type zebrafish larvae and mutant larvae that lack enteric nerves, thus confirming a physiologic role for regulation of smooth muscle contraction at the actin filament.
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影响因子：
2.9
作者：
HORIUCHI, KY;CHACKO, S
通讯作者：
CHACKO, S
影响因子：
4.5
作者：
HAEBERLE, JR;HOTT, JW;HATHAWAY, DR
通讯作者：
HATHAWAY, DR
影响因子：
11
作者：
Kordowska, J;Huang, RJ;Wang, CLA
通讯作者：
Wang, CLA
DOI：
10.1016/0006-291x(86)90426-2
发表时间：
1986-05-14
影响因子：
3.1
作者：
HORIUCHI, KY;MIYATA, H;CHACKO, S
通讯作者：
CHACKO, S
影响因子：
29.4
作者：
He, Wei-Qi;Peng, Ya-Jing;Zhu, Min-Sheng
通讯作者：
Zhu, Min-Sheng