Myoblast migration is prevented by a calpain-dependent accumulation of MARCKS
Myoblast migration is prevented by a calpain-dependent accumulation of MARCKS
复制标题
DOI：
10.1016/j.biolcel.2003.09.005
复制
发表时间：
2003-12-01
影响因子：
2.7
通讯作者：
Cottin, P
中科院分区：
文献类型：
--
作者：
Dedieu, S;Mazères, G;Cottin, P
钙蛋白酶（Calpains），又称钙激活中性半胱氨酸蛋白酶（Neutral cysteine proteins，NCP），是一种重要的生物学活性物质，在信号转导、细胞运动、细胞凋亡、细胞周期调控、肌肉细胞分化等生理和生物学过程中发挥重要作用。关于这最后一点，钙蛋白酶已被证明在早期肌发生过程中起着至关重要的作用。在这项研究中，我们分析了参与钙蛋白酶在一个重要的步骤，肌发生：成肌细胞迁移。我们的研究结果表明，成肌细胞迁移急剧减少时，μ-和m-钙蛋白酶的表达减少。我们还观察到，MARCKS（豆蔻酰化富含丙氨酸的C激酶底物），一种定位于粘着斑部位的蛋白质，当钙蛋白酶的表达水平降低时显著积累。此外，使用佛波醇肉豆蔻酸酯乙酸酯（PKC的激活剂）和质粒携带的全长cDNA的MARCKS或缺乏磷酸化位点域的cDNA片段，我们证明了正常的成肌细胞迁移是依赖于MARCKS磷酸化和本地化。(C)2003年，Elsevier SAS科学与医学版。All rights reserved.
Calpains, also called calcium activated neutral cysteine proteases are presently known to play pivotal roles in physiological and biological phenomena such as signal transduction, cell spreading and motility, apoptosis, regulation of cell cycle and regulation of muscle cell differentiation. Concerning this last point, calpains have been shown to play a crucial role during the earlier myogenesis. In this study we have analyzed the involvement of calpains during an important step of myogenesis: myoblast migration. Our findings show that myoblast migration was drastically reduced when the expression of mu- and m-calpain was decreased. We have also observed that MARCKS (myristoylated alanine rich C kinase substrate), a protein localized at focal adhesion sites, was significantly accumulated when the expression levels of calpains were decreased. Also, using phorbol myristate acetate, (an activator of PKC) and plasmids carrying the full-length cDNA of MARCKS or a cDNA fragment lacking the phosphorylation site domain, we demonstrated that normal myoblast migration is dependent on MARCKS phosphorylation and localization. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.