Cortactin interacts with αDystrobrevin-1 and regulates murine neuromuscular junction morphology

IF 4.5 3区 生物学 Q2 CELL BIOLOGY European journal of cell biology Pub Date : 2024-03-31 DOI:10.1016/j.ejcb.2024.151409
Teresa De Cicco , Marcin Pęziński , Olga Wójcicka , Bhola Shankar Pradhan , Margareta Jabłońska , Klemens Rottner , Tomasz J. Prószyński
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Abstract

Neuromuscular junctions transmit signals from the nervous system to skeletal muscles, triggering their contraction, and their proper organization is essential for breathing and voluntary movements. αDystrobrevin-1 is a cytoplasmic component of the dystrophin-glycoprotein complex and has pivotal functions in regulating the integrity of muscle fibers and neuromuscular junctions. Previous studies identified that αDystrobrevin-1 functions in the organization of the neuromuscular junction and that its phosphorylation in the C-terminus is required in this process. Our proteomic screen identified several putative αDystrobrevin-1 interactors recruited to the Y730 site in phosphorylated and unphosphorylated states. Amongst various actin-modulating proteins, we identified the Arp2/3 complex regulator cortactin. We showed that similarly to αDystrobrevin-1, cortactin is strongly enriched at the neuromuscular postsynaptic machinery and obtained results suggesting that these two proteins interact in cell homogenates and at the neuromuscular junctions. Analysis of synaptic morphology in cortactin knockout mice showed abnormalities in the slow-twitching soleus muscle and not in the fast-twitching tibialis anterior. However, muscle strength examination did not reveal apparent deficits in knockout animals.

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Cortactin 与 αDystrobrevin-1 相互作用并调控小鼠神经肌肉接头形态
神经肌肉接头将信号从神经系统传递到骨骼肌,从而触发肌肉收缩,其正常组织对呼吸和自主运动至关重要。αDystrobrevin-1是肌营养蛋白-糖蛋白复合物的细胞质成分,在调节肌纤维和神经肌肉接头的完整性方面具有关键作用。以前的研究发现,αDystrobrevin-1 在神经肌肉接头的组织中起作用,而且在这一过程中需要其 C 端磷酸化。我们的蛋白质组筛选发现了几种在磷酸化和非磷酸化状态下被招募到 Y730 位点的推定 αDystrobrevin-1 相互作用因子。在各种肌动蛋白调节蛋白中,我们发现了 Arp2/3 复合物调节蛋白 cortactin。我们发现,与αDystrobrevin-1类似,cortactin也在神经肌肉突触后机制中大量富集,研究结果表明,这两种蛋白在细胞匀浆和神经肌肉接头处相互作用。对基因敲除小鼠突触形态的分析表明,慢速肌的比目鱼肌出现异常,而快速肌的胫骨前肌没有异常。然而,肌力检查并未发现基因敲除动物有明显的缺陷。
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来源期刊
European journal of cell biology
European journal of cell biology 生物-细胞生物学
CiteScore
7.30
自引率
1.50%
发文量
80
审稿时长
38 days
期刊介绍: The European Journal of Cell Biology, a journal of experimental cell investigation, publishes reviews, original articles and short communications on the structure, function and macromolecular organization of cells and cell components. Contributions focusing on cellular dynamics, motility and differentiation, particularly if related to cellular biochemistry, molecular biology, immunology, neurobiology, and developmental biology are encouraged. Manuscripts describing significant technical advances are also welcome. In addition, papers dealing with biomedical issues of general interest to cell biologists will be published. Contributions addressing cell biological problems in prokaryotes and plants are also welcome.
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