Maraldi Nadir M, Capanni Cristina, Del Coco Rosalba, Squarzoni Stefano, Columbaro Marta, Mattioli Elisabetta, Lattanzi Giovanna, Manzoli Francesco A
Laboratory of Musculoskeletal Cell Biology, Istituto Ortopedico Rizzoli, Bologna, Italy.
Adv Enzyme Regul. 2011;51(1):246-56. doi: 10.1016/j.advenzreg.2010.09.006. Epub 2010 Oct 28.
Lamin A is a nuclear envelope constituent involved in a group of human disorders, collectively referred to as laminopathies, which include Emery-Dreifuss muscular dystrophy. Because increasing evidence suggests a role of lamin A precursor in nuclear functions, we investigated the processing of prelamin A along muscle differentiation. Both protein levels and cellular localization of prelamin A appears to be modulated during C2C12 mouse myoblasts activation. Similar changes also occur in the expression of two lamin A-binding proteins: emerin and LAP2α. Furthermore prelamin A forms a complex with LAP2α in differentiating myoblasts. Prelamin A accumulation in cycling myoblasts by expressing unprocessable mutants affects LAP2α and PCNA amount and increases caveolin 3 mRNA and protein levels, whilst accumulation of prelamin A in differentiated muscle cells following treatment with a farnesyl transferase inhibitor inhibits caveolin 3 expression. These data provide evidence for a critical role of lamin A precursor in the early steps of muscle cell differentiation. In fact the post-translational processing of prelamin A affects caveolin 3 expression and influences the myoblast differentiation process. Thus, altered lamin A processing could affect myoblast differentiation and/or muscle regeneration and might contribute to the myopathic phenotype.
核纤层蛋白A是核膜的一种组成成分，与一组人类疾病相关，这些疾病统称为核纤层蛋白病，其中包括埃默里-德赖富斯肌营养不良症。由于越来越多的证据表明核纤层蛋白A前体在核功能中发挥作用，我们研究了前体核纤层蛋白A在肌肉分化过程中的加工情况。在C2C12小鼠成肌细胞激活过程中，前体核纤层蛋白A的蛋白质水平和细胞定位似乎都受到了调节。两种核纤层蛋白A结合蛋白emerin和LAP2α的表达也发生了类似变化。此外，在前体成肌细胞分化过程中，前体核纤层蛋白A与LAP2α形成复合物。通过表达不可加工的突变体使前体核纤层蛋白A在循环成肌细胞中积累，会影响LAP2α和增殖细胞核抗原（PCNA）的量，并增加小窝蛋白3的mRNA和蛋白质水平，而在用法尼基转移酶抑制剂处理后，前体核纤层蛋白A在分化的肌肉细胞中积累会抑制小窝蛋白3的表达。这些数据为核纤层蛋白A前体在肌肉细胞分化早期步骤中的关键作用提供了证据。事实上，前体核纤层蛋白A的翻译后加工会影响小窝蛋白3的表达，并影响成肌细胞的分化过程。因此，核纤层蛋白A加工的改变可能会影响成肌细胞的分化和/或肌肉再生，并可能导致肌病表型。
