Cardiac CaMKII activation promotes rapid translocation to its extra-dyadic targets.
Cardiac CaMKII activation promotes rapid translocation to its extra-dyadic targets.
复制标题
DOI：
10.1016/j.yjmcc.2018.10.010
复制
发表时间：
2018-12
影响因子：
5
通讯作者：
Bossuyt J
中科院分区：
文献类型：
--
作者：
Wood BM;Simon M;Galice S;Alim CC;Ferrero M;Pinna NN;Bers DM;Bossuyt J
钙钙调蛋白依赖性蛋白激酶 IIδ (CaMKIIδ) 是心脏电生理、钙 (Ca) 平衡、收缩、转录、心律失常和心力衰竭进展的重要调节因子。 CaMKII 在二元裂隙 Ca 通道口很容易被激活，但由于其低 Ca-钙调蛋白亲和力和假定的固定性，目前尚不清楚 CaMKII 如何在其他已知的额外二元靶点附近被激活。 CaMKII 通常被认为锚定在心肌细胞中，但虽然未经测试，但活性 CaMKII 的移动性可以为心肌细胞中更广泛的靶点磷酸化提供机制。因此，我们测试了成年兔心肌细胞中 CaMKII 的迁移率以及激酶激活对 CaMKII 迁移率的影响。我们使用免疫细胞化学、光漂白后荧光恢复 (FRAP) 和荧光光激活测量了内源性和荧光标记的 CaMKII 的易位。与 CaMKII 锚定在其心肌细胞靶标附近的普遍观点相反，我们发现 CaMKII 在静息肌细胞中具有高度的移动性，其因 Ca 螯合而减慢，并因起搏而加速。在低 [Ca] 时，CaMKII 集中在二联体附近的 Z 线上，但在起搏时散布到整个肌节。 CaMKII 的核交换在起搏和心力衰竭诱导的慢性激活时也得到增强。活性 CaMKII 及其内在记忆的这种动员可能使 CaMKII 在高 [Ca] 区域被激活，然后向更远的肌细胞靶位移动。
Calcium-calmodulin dependent protein kinase IIδ (CaMKIIδ) is an important regulator of cardiac electrophysiology, calcium (Ca) balance, contraction, transcription, arrhythmias and progression to heart failure. CaMKII is readily activated at mouths of dyadic cleft Ca channels, but because of its low Ca-calmodulin affinity and presumed immobility it is less clear how CaMKII gets activated near other known, extra-dyad targets. CaMKII is typically considered to be anchored in cardiomyocytes, but while untested, mobility of active CaMKII could provide a mechanism for broader target phosphorylation in cardiomyocytes. We therefore tested CaMKII mobility and how this is affected by kinase activation in adult rabbit cardiomyocytes. We measured translocation of both endogenous and fluorescence-tagged CaMKII using immunocytochemistry, fluorescence recovery after photobleach (FRAP) and photoactivation of fluorescence. In contrast to the prevailing view that CaMKII is anchored near its myocyte targets, we found CaMKII to be highly mobile in resting myocytes, which was slowed by Ca chelation and accelerated by pacing. At low [Ca], CaMKII was concentrated at Z-lines near the dyad but spread throughout the sarcomere upon pacing. Nuclear exchange of CaMKII was also enhanced upon pacing- and heart failure-induced chronic activation. This mobilization of active CaMKII and its intrinsic memory may allow CaMKII to be activated in high [Ca] regions and then move towards more distant myocyte target sites.
登录
查看更多内容
DOI：
10.1161/circep.117.005852
发表时间：
2018-03
期刊：
Circulation. Arrhythmia and electrophysiology
影响因子：
--
作者：
Hegyi B;Bossuyt J;Ginsburg KS;Mendoza LM;Talken L;Ferrier WT;Pogwizd SM;Izu LT;Chen-Izu Y;Bers DM
通讯作者：
Bers DM
CAMKII将Ca2+通道的camkii tethers建立，建立了Ca2+信号的本地和专用集成商进行便利。
影响因子：
7.8
作者：
Hudmon, A;Schulman, H;Kim, J;Maltez, JM;Tsien, RW;Pitt, GS
通讯作者：
Pitt, GS
影响因子：
18.2
作者：
Fischer, Thomas H.;Eiringhaus, Joerg;Sossalla, Samuel
通讯作者：
Sossalla, Samuel
影响因子：
9.5
作者：
Kreusser, Michael M.;Lehmann, Lorenz H.;Backs, Johannes
通讯作者：
Backs, Johannes
影响因子：
64.5
作者：
Erickson, Jeffrey R.;Joiner, Mei-ling A.;Anderson, Mark E.
通讯作者：
Anderson, Mark E.