Jafferali Mohammed Hakim, Figueroa Ricardo A, Hasan Mehedi, Hallberg Einar
Department of Neurochemistry, Stockholm University, Svante Arrhenius väg 16B, SE-106 91, Stockholm, Sweden.
Sci Rep. 2017 Nov 30;7(1):16655. doi: 10.1038/s41598-017-16746-y.
Muscles are developed and regenerated in a differentiation process called myogenesis, which involves components of the nuclear envelope. We have investigated Samp1 (Spindle Associated Membrane Protein 1), a transmembrane nuclear envelope protein, which interacts with emerin and lamin A, both of which are linked to Emery-Dreifuss muscular dystrophy (EDMD). We found that the levels of Samp1 increased seven-fold during differentiation of mouse C2C12 muscle progenitor cells. To test if Samp1 could have a role in myogenesis we developed stable C2C12 knockdown cell lines expressing short hairpin RNA targeting Samp1 expression. The Samp1 depleted C2C12 cells displayed normal mobility and normal distribution of emerin and lamin A. However, Samp1 depletion increased ERK signaling and completely blocked differentiation of C2C12 cells, which failed to express myogenic marker proteins and failed to form myotubes. The block in myogenesis in Samp1 depleted cells was completely rescued by ectopic expression of RNAi resistant human Samp1, showing that Samp1 is required for muscle differentiation.
肌肉在一个称为肌生成的分化过程中发育和再生，这个过程涉及核膜的组成部分。我们研究了Samp1（纺锤体相关膜蛋白1），一种跨膜核膜蛋白，它与emerin和核纤层蛋白A相互作用，而这两种蛋白都与Emery-Dreifuss肌营养不良症（EDMD）有关。我们发现，在小鼠C2C12肌肉祖细胞分化过程中，Samp1的水平增加了七倍。为了测试Samp1是否在肌生成中发挥作用，我们构建了稳定的C2C12敲低细胞系，这些细胞系表达靶向Samp1表达的短发夹RNA。Samp1缺失的C2C12细胞表现出正常的迁移能力以及emerin和核纤层蛋白A的正常分布。然而，Samp1缺失会增加ERK信号传导，并完全阻断C2C12细胞的分化，这些细胞无法表达肌源性标记蛋白，也无法形成肌管。通过异位表达对RNAi有抗性的人Samp1，完全挽救了Samp1缺失细胞中肌生成的阻断，表明Samp1是肌肉分化所必需的。
