The intermediate filament protein, synemin, is an AKAP in the heart.
The intermediate filament protein, synemin, is an AKAP in the heart.
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中间丝蛋白 Synemin 是心脏中的 AKAP。
DOI：
10.1016/j.abb.2006.06.010
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发表时间：
2006
影响因子：
3.9
通讯作者：
Bond,Meredith
中科院分区：
文献类型：
--
作者：
Russell,MaryA;Lund,LindaM;Haber,Roy;McKeegan,Kathleen;Cianciola,Nicholas;Bond,Meredith
蛋白激酶A锚定蛋白(AKAPs)靶向蛋白激酶A(PKA)有助于PKA信号通路的高度特异性。PKA对肌丝和细胞骨架蛋白的磷酸化可能调节心脏病期间的肌原纤维形成和心肌细胞重塑；然而，已知的心脏AKAP并不局限于这些区域。为了鉴定针对细胞骨架或肌丝的新的PKA结合蛋白，我们筛选了一个人心脏cDNA文库，中间丝蛋白SYNMEN被鉴定为一种可能的RII(PKA调节亚单位II)结合蛋白。预测的RII结合区发生突变，导致RII结合缺失。此外，在SW13/Cl.1-VIM+细胞中，SYNMENT与RII共定位，并与成年大鼠心肌细胞中的RII免疫共沉淀。Synmin与RII和结蛋白在成人心脏中定位于Z线水平，而新生心肌细胞则表现出不同的同步素和结蛋白定位。定量Western印迹还显示，在衰竭的心脏中存在显著更多的同步蛋白。我们认为Synmin在成人和新生儿心肌细胞中提供了PKA的时间和空间靶向。
Targeting of protein kinase A (PKA) by A-kinase anchoring proteins (AKAPs) contributes to high specificity of PKA signaling pathways. PKA phosphorylation of myofilament and cytoskeletal proteins may regulate myofibrillogenesis and myocyte remodeling during heart disease; however, known cardiac AKAPs do not localize to these regions. To identify novel AKAPs which target PKA to the cytoskeleton or myofilaments, a human heart cDNA library was screened and the intermediate filament (IF) protein, synemin, was identified as a putative RII (PKA regulatory subunit type II) binding protein. A predicted RII binding region was mutated and resulted in loss of RII binding. Furthermore, synemin co-localized with RII in SW13/cl.1-vim+ cells and co-immunoprecipitated with RII from adult rat cardiomyocytes. Synemin was localized at the level of Z-lines with RII and desmin in adult hearts, however, neonatal cardiomyocytes showed differential synemin and desmin localization. Quantitative Western blots also showed significantly more synemin was present in failing human hearts. We propose that synemin provides temporal and spatial targeting of PKA in adult and neonatal cardiac myocytes.