Interdisciplinary Stem Cell Institute, Department of Pediatrics, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
J Biomed Sci. 2013 Aug 3;20(1):56. doi: 10.1186/1423-0127-20-56.
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.
CIP4 是一种支架蛋白，可调节细胞膜的变形和管状化、肌动蛋白细胞骨架的组织、生长因子受体的内吞作用以及囊泡运输。尽管 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，CIP4 在新生大鼠心室肌细胞中的表达对于 α-肾上腺素能激动剂苯肾上腺素、IL-6 细胞因子白血病抑制因子和胎牛血清诱导的非有丝分裂、肥大生长是必需的，如通过形态计量学、肥大标志物心钠素的免疫细胞化学和用于从头蛋白质合成的 [3H]亮氨酸掺入来测定。这种需求与肥大刺激诱导 CIP4 表达一致。用重组 CIP4 蛋白表达而不是用缺乏负责 CIP4 细胞内定位的 N 端 FCH 结构域的突变体表达可挽救 CIP4 小干扰寡核苷酸 (siRNA) 对心肌细胞肥大的抑制作用。
这些结果表明，CIP4 在控制心脏病中心肌细胞生长的细胞内肥大信号转导网络中发挥重要作用。
