Tsukamoto Yoshiyuki, Hijiya Naoki, Yano Shinji, Yokoyama Shigeo, Nakada Chisato, Uchida Tomohisa, Matsuura Keiko, Moriyama Masatsugu
Department of Molecular Pathology, Faculty of Medicine, Oita University, Yufu-city, Oita, 879-5593, Japan.
Histochem Cell Biol. 2008 Jan;129(1):55-64. doi: 10.1007/s00418-007-0348-9. Epub 2007 Oct 10.
Ankyrin-repeat protein with a PEST motif and a proline-rich region (Arpp), also designated as Ankrd2, is a member of the muscle ankyrin repeat proteins (MARPs), which have been proposed to be involved in muscle stress response pathways. Arpp/Ankrd2 is localized mainly in the I-band of striated muscle. However, it has recently been reported that Arpp/Ankrd2 can interact with nuclear proteins, such as premyelocytic leukemia protein (PML), p53 and YB-1 in vitro. In this study, to determine whether nuclear accumulation of Arpp/Ankrd2 actually occurs, we performed an immunohistochemical investigation of gastrocnemius muscles that had been injured by injection of cardiotoxin or contact with dry ice. We found that Arpp/Ankrd2 accumulated in the nuclei of myofibers located adjacent to severely damaged myofibers after muscle injury. Double-labeled immunohistochemistry revealed that Arpp/Ankrd2 accumulated in the nuclei of sarcomere-damaged myofibers. Furthermore, we found that Arpp/Ankrd2 tended to be localized in euchromatin where genes are transcriptionally activated. Based on these findings, we suggest that Arpp/Ankrd2 may translocate from the I-band to the nucleus in response to muscle damage and may participate in the regulation of gene expression.
含有PEST基序和富含脯氨酸区域的锚蛋白重复序列蛋白(Arpp),也被称为Ankrd2,是肌肉锚蛋白重复序列蛋白(MARPs)家族的一员,有人提出该家族参与肌肉应激反应途径。Arpp/Ankrd2主要定位于横纹肌的I带。然而,最近有报道称,Arpp/Ankrd2在体外可与核蛋白相互作用,如早幼粒细胞白血病蛋白(PML)、p53和YB-1。在本研究中,为了确定Arpp/Ankrd2是否真的会发生核内积聚,我们对注射了心脏毒素或接触干冰而受损的腓肠肌进行了免疫组织化学研究。我们发现,肌肉损伤后,Arpp/Ankrd2在紧邻严重受损肌纤维的肌纤维核内积聚。双重标记免疫组织化学显示,Arpp/Ankrd2在肌节受损的肌纤维核内积聚。此外,我们发现Arpp/Ankrd2倾向于定位于基因转录激活的常染色质中。基于这些发现,我们认为Arpp/Ankrd2可能会在肌肉损伤时从I带转运至细胞核,并可能参与基因表达的调控。