Phenotypic consequences of beta1-tubulin expression and MAP4 decoration of microtubules in adult cardiocytes.
Phenotypic consequences of beta1-tubulin expression and MAP4 decoration of microtubules in adult cardiocytes.
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成人心肌细胞中微管 β1-微管蛋白表达和 MAP4 装饰的表型后果。
DOI：
10.1152/ajpheart.00396.2003
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Cooper4th,George
中科院分区：
文献类型：
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作者：
Takahashi,Masaru;Shiraishi,Hirokazu;Ishibashi,Yuji;Blade,KristieL;McDermott,PaulJ;Menick,DonaldR;Kuppuswamy,Dhandapani;Cooper4th,George
在压力超负荷的心脏肥大中，微管网络致密化是收缩功能障碍的原因之一。心肌肥大伴随着 β1-微管蛋白（而不是组成型 β4-微管蛋白）和微管相关蛋白 (MAP)4 的心脏转录上调，并且 MAP4 广泛修饰微管。由于 MAP4 稳定微管，并且由于 β-微管蛋白的异构体可变羧基末端与 MAP4 结合，我们希望确定这些蛋白质中的一种或两种是否对心脏微管网络致密化具有病因学意义。使用编码β1-微管蛋白、β4-微管蛋白和MAP4的重组腺病毒来感染分离的心肌细胞。 MAP4 过度表达导致微管蛋白二聚体向聚合部分转移，并形成致密、稳定的微管网络。过表达的 β1- 或 β4- 微管蛋白对这些变量既没有任何独立的影响，也没有任何与同时过表达的 MAP4 相加的影响。心脏过度表达 β1-微管蛋白或 MAP4 的转基因小鼠的结果是证实性的，但与分离心肌细胞中短暂的腺病毒介导的 MAP4 过度表达的影响不同，MAP4 转基因心脏显示总 α- 和 β- 微管蛋白显着增加。因此，MAP4 过表达导致微管蛋白表达增加、稳定微管的形成以及微管网络特性的改变，因此 MAP4 上调可能是压力超载、肥大的心肌细胞形成致密、稳定的微管网络特征的原因之一。
In pressure-overload cardiac hypertrophy, microtubule network densification is one cause of contractile dysfunction. Cardiac transcriptional upregulation of β1-tubulin rather than the constitutive β4-tubulin and of microtubule-associated protein (MAP)4 accompanies hypertrophy, with extensive microtubule decoration by MAP4. Because MAP4 stabilizes microtubules, and because the isoform-variable carboxy terminus of β-tubulin binds to MAP4, we wished to determine whether one or both of these proteins has etiologic significance for cardiac microtubule network densification. Recombinant adenoviruses encoding β1-tubulin, β4-tubulin, and MAP4 were used to infect isolated cardiocytes. Overexpressed MAP4 caused a shift of tubulin dimers to the polymerized fraction and formation of a dense, stable microtubule network. Overexpressed β1- or β4-tubulin had neither any independent effect on these variables nor any effect additive to that of simultaneously overexpressed MAP4. Results from transgenic mice with cardiac overexpression of β1-tubulin or MAP4 were confirmatory, but unlike the effects of brief adenovirus-mediated MAP4 overexpression in isolated cardiocytes, MAP4 transgenic hearts showed a marked increase in total α- and β-tubulin. Thus MAP4 overexpression caused increased tubulin expression, formation of stable microtubules, and altered microtubule network properties, such that MAP4 upregulation may be one cause for the dense, stable microtubule network characteristic of pressure-overloaded, hypertrophied cardiocytes.