Ermanoska Biljana, Baets Jonathan, Rodal Avital A
Department of Biology, Brandeis University, Waltham, MA.
Neuromuscular Reference Centre, Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
bioRxiv. 2025 Jan 26:2023.11.10.566609. doi: 10.1101/2023.11.10.566609.
Neuromuscular junctions (NMJs) are evolutionarily ancient, specialized contacts between neurons and muscles. They endure mechanical strain from muscle contractions throughout life, but cellular mechanisms for managing this stress remain unclear. Here we identify a novel actomyosin structure at larval NMJs, consisting of a long-lived, low-turnover presynaptic actin core that co-localizes with non-muscle myosin II (NMII). This core is likely to have contractile properties, as manipulating neuronal NMII levels or activity disrupts its organization. Intriguingly, depleting neuronal NMII triggered changes in postsynaptic muscle NMII levels and organization near synapses, suggesting transsynaptic propagation of actomyosin rearrangements. We also found reduced levels of Integrin adhesion receptors both pre- and postsynaptically upon NMII knockdown, indicating disrupted neuron-muscle connections. Mechanical severing of axons caused similar actin core fragmentation and Integrin loss to NMII depletion, suggesting this structure responds to tension. Our findings reveal a presynaptic actomyosin assembly that maintains mechanical continuity between neurons and muscle, possibly facilitating mechanotransduction at the NMJ via Integrin-mediated adhesion.
神经肌肉接头（NMJs）是神经元与肌肉之间进化上古老的特殊连接。它们在整个生命过程中承受着肌肉收缩产生的机械张力，但应对这种压力的细胞机制仍不清楚。在这里，我们在幼虫神经肌肉接头上发现了一种新的肌动球蛋白结构，它由一个长寿命、低周转率的突触前肌动蛋白核心组成，该核心与非肌肉肌球蛋白II（NMII）共定位。这个核心可能具有收缩特性，因为操纵神经元NMII水平或活性会破坏其组织。有趣的是，耗尽神经元NMII会引发突触后肌肉NMII水平和突触附近组织的变化，表明肌动球蛋白重排的跨突触传播。我们还发现，在NMII敲低后，突触前和突触后的整合素粘附受体水平均降低，表明神经元与肌肉的连接被破坏。轴突的机械切断导致与NMII耗尽类似的肌动蛋白核心碎片化和整合素丢失，表明这种结构对张力有反应。我们的研究结果揭示了一种突触前肌动球蛋白组装体，它维持着神经元与肌肉之间的机械连续性，可能通过整合素介导的粘附促进神经肌肉接头处的机械转导。
