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Abstract：
Striated muscle laminopathies are cardiac and skeletal muscle conditions caused by mutations in the lamin A/C gene (LMNA). LMNA codes for the A-type lamins, which are nuclear intermediate filaments that maintain the nuclear structure and nuclear processes such as gene expression. Protein kinase C alpha (PKC-α) interacts with lamin A/C and with several lamin A/C partners involved in striated muscle laminopathies. To determine PKC-α\'s involvement in muscular laminopathies, PKC-α\'s localization, activation, and interactions with the A-type lamins were examined in various cell types expressing pathogenic lamin A/C mutations. The results showed aberrant nuclear PKC-α cellular distribution in mutant cells compared to WT. PKC-α activation (phos-PKC-α) was decreased or unchanged in the studied cells expressing LMNA mutations, and the activation of its downstream targets, ERK 1/2, paralleled PKC-α activation alteration. Furthermore, the phos-PKC-α-lamin A/C proximity was altered. Overall, the data showed that PKC-α localization, activation, and proximity with lamin A/C were affected by certain pathogenic LMNA mutations, suggesting PKC-α involvement in striated muscle laminopathies.
摘要：
横纹肌层肌病是由层粘连蛋白A/C基因（LMNA）突变引起的心脏和骨骼肌疾病。A型薄片的LMNA代码，是核中间丝，维持核结构和核过程，如基因表达。蛋白激酶Cα（PKC-α）与层粘连蛋白A/C以及涉及横纹肌层粘连蛋白病的几个层粘连蛋白A/C伴侣相互作用。为了确定PKC-α在肌层肌病中的参与，PKC-α的定位，激活,在表达致病性层粘连蛋白A/C突变的各种细胞类型中检查了与A型层粘连蛋白的相互作用。结果显示与WT相比,突变细胞中异常的核PKC-α细胞分布。在表达LMNA突变的研究细胞中，PKC-α激活（phos-PKC-α）降低或不变，以及其下游目标的激活，ERK1/2，平行PKC-α激活改变。此外，phos-PKC-α-层粘连蛋白A/C接近度改变。总的来说,数据显示PKC-α定位，激活,与层粘连蛋白A/C的接近度受到某些致病性LMNA突变的影响，提示PKC-α参与横纹肌层病变。
