Differential regulation of Tbx5 protein expression and sub-cellular localization during heart development
Differential regulation of Tbx5 protein expression and sub-cellular localization during heart development
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DOI：
10.1016/j.ydbio.2006.09.023
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发表时间：
2007-02-01
影响因子：
2.7
通讯作者：
Simon, Hans-Georg
中科院分区：
文献类型：
--
作者：
Bimber, Benjamin;Dettman, Robert W.;Simon, Hans-Georg
T-box转录因子Tbx5可以与Nkx2.5和Gata4转录因子相互作用，协同调节细胞核中的心脏特异性基因。虽然Tbx5的核作用是明确定义的，我们以前已经表明，Tbx5穿梭从细胞核到细胞质的网站，形成一个复合物与PDZ-LIM蛋白LMP4的肌动蛋白细胞骨架。在这项研究中，使用一系列发育中的鸡心，我们提供了第一个证据，差异Tbx5蛋白表达和亚细胞定位在心脏发生。在组织水平上，我们显示了时间和空间限制的Tbx5与LMP4的共表达。在共表达LMP4和Tbx5的细胞中，我们证明了Tbx5在房室垫中从完全核到核和胞质表达的动态再定位。此外，在冠状动脉血管的发展，我们显示出独家的Tbx5的细胞质定位，表明Tbx5在细胞质中的功能。此外，我们发现了Tbx5和LMP4在心外膜组织中表达的未知调节，表明Tbx5在心外膜形成中的特定作用。这些研究提供了LMP4/Tbx5蛋白相互作用的体内意义，表明Tbx5的细胞核和细胞质作用。细胞核和细胞质位点之间的穿梭揭示了Tbx转录因子在鸡心脏发育中调控的新机制，为更好地理解与TBX5突变相关的手/心脏出生缺陷的分子基础提供了新的见解。(c)2006爱思唯尔公司All rights reserved.
The T-box transcription factor Tbx5 can interact with Nkx2.5 and Gata4 transcription factors to synergistically regulate heart-specific genes in the nucleus. While a nuclear role for Tbx5 is clearly defined, we have previously shown that Tbx5 shuttles from nuclear to cytoplasmic sites, forming a complex with the PDZ-LIM protein LMP4 on the actin cytoskeleton. In this study, using a developmental series of chicken hearts, we provide the first evidence for differential Tbx5 protein expression and sub-cellular localization during cardiogenesis. At the tissue level, we show temporally and spatially restricted Tbx5 co-expression with LMP4. In cells co-expressing LMP4 and Tbx5 we demonstrate dynamic Tbx5 relocalization from exclusively nuclear to nuclear and cytoplasmic expression in the atrio-ventricular cushion. Furthermore, in coronary vessel development we show exclusive cytoplasmic localization of Tbx5, indicating a function for Tbx5 in the cytoplasm. In addition, we discover unknown regulation of Tbx5 and LMP4 expression in epicardial tissue, suggesting a specific role for Tbx5 in epicardial formation. These studies provide in vivo significance of the LMP4/Tbx5 protein interaction, suggesting both nuclear and cytoplasmic roles for Tbx5. The shuttling between nuclear and cytoplasmic sites reveals a novel mechanism for Tbx transcription factor regulation in chicken heart development allowing new insights for a better understanding of the molecular basis of hand/heart birth defects associated with TBX5 mutations. (c) 2006 Elsevier Inc. All rights reserved.