CAP2 is a regulator of actin pointed end dynamics and myofibrillogenesis in cardiac muscle.
CAP2 is a regulator of actin pointed end dynamics and myofibrillogenesis in cardiac muscle.
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DOI：
10.1038/s42003-021-01893-w
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发表时间：
2021-03-19
影响因子：
5.9
通讯作者：
Gregorio CC
中科院分区：
文献类型：
--
作者：
Colpan M;Iwanski J;Gregorio CC
以肌动蛋白为基础的细丝的精确组装对肌肉收缩至关重要。肌动蛋白在细丝尖端的动力学失调导致骨骼肌病和心肌病。在这里，我们发现腺酰环化酶相关蛋白2(CAP2)是心肌细丝尖端的一种独特成分。CAP2在心肌细胞中具有重要的功能，因为它解聚并抑制肌动蛋白掺入细丝。与其他尖端蛋白不同的是，CAP2的S功能不是被原肌球蛋白增强而是被抑制，它不直接控制细丝长度。此外，CAP2通过调节肌节前肌动蛋白的组装和调节成熟细丝中的α-肌动蛋白组成，在心肌细胞的成熟过程中发挥重要作用。CAP2的S多功能角色的确定为我们理解细丝结构是如何在横纹肌中调控提供了缺失的一环，它揭示了除了Tmod1和Lmod2之外，还有其他因素调节细丝尖端的肌动蛋白动力学。格雷戈里奥、科尔潘和Iwanski描述了环化相关蛋白2(CAP2)在调节心肌细胞内肌动蛋白细丝的组织和动态中的作用。他们表明，CAP2解聚并抑制肌动蛋白掺入细丝，也是心肌细胞成熟所必需的。
The precise assembly of actin-based thin filaments is crucial for muscle contraction. Dysregulation of actin dynamics at thin filament pointed ends results in skeletal and cardiac myopathies. Here, we discovered adenylyl cyclase-associated protein 2 (CAP2) as a unique component of thin filament pointed ends in cardiac muscle. CAP2 has critical functions in cardiomyocytes as it depolymerizes and inhibits actin incorporation into thin filaments. Strikingly distinct from other pointed-end proteins, CAP2’s function is not enhanced but inhibited by tropomyosin and it does not directly control thin filament lengths. Furthermore, CAP2 plays an essential role in cardiomyocyte maturation by modulating pre-sarcomeric actin assembly and regulating α-actin composition in mature thin filaments. Identification of CAP2’s multifunctional roles provides missing links in our understanding of how thin filament architecture is regulated in striated muscle and it reveals there are additional factors, beyond Tmod1 and Lmod2, that modulate actin dynamics at thin filament pointed ends. Gregorio, Colpan and Iwanski characterize the role of cyclase-associated protein 2 (CAP2) in regulating the organization and dynamics of actin filaments within cardiomyocytes. They show that CAP2 depolymerizes and inhibits actin incorporation into thin filaments and is also required for cardiomyocyte maturation.
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影响因子：
3.3
作者：
Bertling, E;Hotulainen, P;Lappalainen, P
通讯作者：
Lappalainen, P
影响因子：
2.9
作者：
Dodatko, T;Fedorov, AA;Almo, SC
通讯作者：
Almo, SC
影响因子：
1.3
作者：
Celestino-Soper PB;Skinner C;Schroer R;Eng P;Shenai J;Nowaczyk MM;Terespolsky D;Cushing D;Patel GS;Immken L;Willis A;Wiszniewska J;Matalon R;Rosenfeld JA;Stevenson RE;Kang SH;Cheung SW;Beaudet AL;Stankiewicz P
通讯作者：
Stankiewicz P
影响因子：
2.7
作者：
Colpan M;Moroz NA;Kostyukova AS
通讯作者：
Kostyukova AS
影响因子：
3.9
作者：
Colpan, Mert;Moroz, Natalia A.;Kostyukova, Alla S.
通讯作者：
Kostyukova, Alla S.