The actin associated protein palladin is important for the early smooth muscle cell differentiation.
The actin associated protein palladin is important for the early smooth muscle cell differentiation.
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DOI：
10.1371/journal.pone.0012823
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发表时间：
2010-09-22
期刊：
影响因子：
3.7
通讯作者：
Somlyo AV
中科院分区：
文献类型：
--
作者：
Jin L;Gan Q;Zieba BJ;Goicoechea SM;Owens GK;Otey CA;Somlyo AV
Palladin 是一种肌动蛋白相关蛋白，在调节细胞粘附和细胞运动方面发挥着重要作用。 Palladin 对于发育很重要，因为敲除小鼠体内会导致胚胎死亡，但其在脉管系统发育中的作用尚不清楚。我们已经证明，palladin 对于平滑肌细胞 (SMC) 标记基因的表达和在 Palladin 缺陷的 SMC 中响应激动剂刺激的力量发育至关重要。该研究的目的是确定 Palladin 调节 SMC 标记基因表达能力的分子机制。结果表明，在视黄酸 (RA) 诱导分化后，A404 细胞系中帕拉丁表达迅速被诱导。用siRNA抑制palladin表达会抑制RA诱导的SMC分化基因SM α-肌动蛋白（SMA）和SM22的表达，而palladin的过度表达会诱导SMC基因表达。染色质免疫沉淀试验提供了 Palladin 与 SMC 基因结合的证据，而免疫共沉淀试验也显示 Palladin 与心肌相关转录因子 (MRTF) 结合。内源性 Palladin 在细胞核中成像，随着细霉素处理而增加，并且 Palladin 的羧基末端与细胞核中的 MRTF 共定位。结果支持这样的模型，其中palladin通过调节SMC标记基因的CArG-SRF-MRTF依赖性转录以及先前发表的还通过肌动蛋白动力学来促进SMC分化。最后，在 E11.5 Palladin 无效小鼠胚胎中，血管壁中 SMA 和 SM22 mRNA 和蛋白的表达降低。综上所述，我们的研究结果表明，palladin 在发育中的脉管系统中 SMC 的分化中发挥着关键作用。
Palladin, an actin associated protein, plays a significant role in regulating cell adhesion and cell motility. Palladin is important for development, as knockdown in mice is embryonic lethal, yet its role in the development of the vasculature is unknown. We have shown that palladin is essential for the expression of smooth muscle cells (SMC) marker genes and force development in response to agonist stimulation in palladin deficient SMCs. The goal of the study was to determine the molecular mechanisms underlying palladin's ability to regulate the expression of SMC marker genes. Results showed that palladin expression was rapidly induced in an A404 cell line upon retinoic acid (RA) induced differentiation. Suppression of palladin expression with siRNAs inhibited the expression of RA induced SMC differentiation genes, SM α-actin (SMA) and SM22, whereas over-expression of palladin induced SMC gene expression. Chromatin immunoprecipitation assays provided evidence that palladin bound to SMC genes, whereas co-immunoprecipitation assays also showed binding of palladin to myocardin related transcription factors (MRTFs). Endogenous palladin was imaged in the nucleus, increased with leptomycin treatment and the carboxyl-termini of palladin co-localized with MRTFs in the nucleus. Results support a model wherein palladin contributes to SMC differentiation through regulation of CArG-SRF-MRTF dependent transcription of SMC marker genes and as previously published, also through actin dynamics. Finally, in E11.5 palladin null mouse embryos, the expression of SMA and SM22 mRNA and protein is decreased in the vessel wall. Taken together, our findings suggest that palladin plays a key role in the differentiation of SMCs in the developing vasculature.
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影响因子：
2.7
作者：
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通讯作者：
Somlyo, Avril V.
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