Miller Melanie K, Bang Marie-Louise, Witt Christian C, Labeit Dietmar, Trombitas Charles, Watanabe Kaori, Granzier Henk, McElhinny Abigail S, Gregorio Carol C, Labeit Siegfried
Department of Cell Biology and Anatomy, University of Arizona, Tucson, AZ 85724, USA.
J Mol Biol. 2003 Nov 7;333(5):951-64. doi: 10.1016/j.jmb.2003.09.012.
CARP, ankrd-2/Arpp, and DARP, are three members of a conserved gene family, referred to here as MARPs (muscle ankyrin repeat proteins). The expression of MARPs is induced upon injury and hypertrophy (CARP), stretch or denervation (ankrd2/Arpp), and during recovery following starvation (DARP), suggesting that they are involved in muscle stress response pathways. Here, we show that MARP family members contain within their ankyrin repeat region a binding site for the myofibrillar elastic protein titin. Within the myofibril, MARPs, myopalladin, and the calpain protease p94 appear to be components of a titin N2A-based signaling complex. Ultrastructural studies demonstrated that all three endogenous MARP proteins co-localize with I-band titin N2A epitopes in adult heart muscle tissues. In cultured fetal rat cardiac myocytes, passive stretch induced differential distribution patterns of CARP and DARP: staining for both proteins was increased in the nucleus and at the I-band region of myofibrils, while DARP staining also increased at intercalated discs. We speculate that the myofibrillar MARPs are regulated by stretch, and that this links titin-N2A-based myofibrillar stress/strain signals to a MARP-based regulation of muscle gene expression.
CARP、ankrd-2/Arpp和DARP是一个保守基因家族的三个成员，在这里被称为MARPs（肌肉锚蛋白重复蛋白）。MARPs的表达在损伤和肥大（CARP）、拉伸或去神经支配（ankrd2/Arpp）时以及饥饿后的恢复过程中（DARP）被诱导，这表明它们参与了肌肉应激反应途径。在这里，我们表明MARP家族成员在其锚蛋白重复区域内含有肌原纤维弹性蛋白肌联蛋白的一个结合位点。在肌原纤维内，MARPs、肌 palladin和钙蛋白酶p94似乎是基于肌联蛋白N2A的信号复合物的组成部分。超微结构研究表明，所有三种内源性MARP蛋白在成年心脏肌肉组织中与I带肌联蛋白N2A表位共定位。在培养的胎鼠心肌细胞中，被动拉伸诱导了CARP和DARP的不同分布模式：两种蛋白在细胞核和肌原纤维的I带区域的染色增加，而DARP在闰盘处的染色也增加。我们推测肌原纤维MARPs受拉伸调节，并且这将基于肌联蛋白-N2A的肌原纤维应力/应变信号与基于MARP的肌肉基因表达调节联系起来。
