Université Bordeaux 1, Unité Protéolyse Croissance et Développement Musculaire, Institut National de la Recherche Agronomique, USC 2009, Avenue des Facultés, F-33405 Talence, France.
J Biol Chem. 2010 Apr 23;285(17):12670-83. doi: 10.1074/jbc.M109.063966. Epub 2010 Feb 5.
Calpain 3 is a calcium-dependent cysteine protease that is primarily expressed in skeletal muscle and is implicated in limb girdle muscular dystrophy type 2A. To date, its best characterized function is located within the sarcomere, but this protease is found in other cellular compartments, which suggests that it exerts multiple roles. Here, we present evidence that calpain 3 is involved in the myogenic differentiation process. In the course of in vitro culture of myoblasts to fully differentiated myotubes, a population of quiescent undifferentiated "reserve cells" are maintained. These reserve cells are closely related to satellite cells responsible for adult muscle regeneration. In the present work, we observe that reserve cells express higher levels of endogenous Capn3 mRNA than proliferating myoblasts. We show that calpain 3 participates in the establishment of the pool of reserve cells by decreasing the transcriptional activity of the key myogenic regulator MyoD via proteolysis independently of the ubiquitin-proteasome degradation pathway. Our results identify calpain 3 as a potential new player in the muscular regeneration process by promoting renewal of the satellite cell compartment.
钙蛋白酶 3 是一种钙依赖性半胱氨酸蛋白酶，主要表达于骨骼肌，与 2A 型肢带型肌营养不良症有关。迄今为止，其最主要的功能被认为位于肌节内，但这种蛋白酶还存在于其他细胞区室中，这表明它具有多种作用。在这里，我们提供了证据表明钙蛋白酶 3 参与了成肌分化过程。在体外培养成肌细胞分化为完全分化的肌管过程中，维持了一群静止的未分化“储备细胞”。这些储备细胞与负责成年肌肉再生的卫星细胞密切相关。在本工作中，我们观察到储备细胞表达的内源性 Capn3 mRNA 水平高于增殖的成肌细胞。我们表明，钙蛋白酶 3 通过蛋白水解作用参与储备细胞池的建立，该作用独立于泛素-蛋白酶体降解途径，降低了关键成肌调节因子 MyoD 的转录活性。我们的结果表明，钙蛋白酶 3 通过促进卫星细胞区室的更新，成为肌肉再生过程中的一个潜在的新角色。
