CIP4 is required for the hypertrophic growth of neonatal cardiac myocytes.
CIP4 is required for the hypertrophic growth of neonatal cardiac myocytes.
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DOI：
10.1186/1423-0127-20-56
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发表时间：
2013-08-03
影响因子：
11
通讯作者：
Kapiloff MS
中科院分区：
文献类型：
--
作者：
Rusconi F;Thakur H;Li J;Kapiloff MS
CIP4是一种支架蛋白，调节膜变形和管状、肌动蛋白细胞骨架的组织、生长因子受体的内吞作用和囊泡运输。虽然CIP4在心脏中表达，但尚未研究其在心肌细胞中的潜在功能。我们现在通过RNA干扰表明，新生儿大鼠心室肌细胞中CIP4的表达是α-肾上腺素激动剂苯肾上腺素、IL-6细胞因子白血病抑制因子和胎牛血清诱导非有丝分裂性肥厚生长所必需的，使用形态测定法、免疫细胞化学检测肥厚标记物心房利钠因子和[3H]亮氨酸掺入检测新生蛋白合成。这一要求与肥厚刺激诱导CIP4表达一致。CIP4小干扰寡核苷酸（siRNA）对肌细胞肥大的抑制作用可以通过表达重组CIP4蛋白来恢复，但不能通过缺乏负责CIP4细胞内定位的n端FCH结构域的突变体来恢复。这些结果表明，CIP4在心脏病中控制心肌细胞生长的细胞内肥厚信号转导网络中起着重要作用。
CIP4 is a scaffold protein that regulates membrane deformation and tubulation, organization of the actin cytoskeleton, endocytosis of growth factor receptors, and vesicle trafficking. Although expressed in the heart, CIP4 has not been studied with regards to its potential function in cardiac myocytes. We now show using RNA interference that CIP4 expression in neonatal rat ventricular myocytes is required for the induction of non-mitotic, hypertrophic growth by the α-adrenergic agonist phenylephrine, the IL-6 cytokine leukemia inhibitor factor, and fetal bovine serum, as assayed using morphometry, immunocytochemistry for the hypertrophic marker atrial natriuretic factor and [3H]leucine incorporation for de novo protein synthesis. This requirement was consistent with the induction of CIP4 expression by hypertrophic stimulation. The inhibition of myocyte hypertrophy by CIP4 small interfering oligonucleotides (siRNA) was rescued by expression of a recombinant CIP4 protein, but not by a mutant lacking the N-terminal FCH domain responsible for CIP4 intracellular localization. These results imply that CIP4 plays a significant role in the intracellular hypertrophic signal transduction network that controls the growth of cardiac myocytes in heart disease.
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