Hastings Robert Louis, Boyce William, Juros Devin, Kim Jinho, Khan Zaid, Sethi Aatish, Valdez Gregorio
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA.
Center for Translational Neuroscience, Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, RI, USA.
J Mol Neurosci. 2025 Sep 4;75(3):113. doi: 10.1007/s12031-025-02406-8.
Collagen type XX alpha 1 (COL20A1) was recently found to be highly concentrated in perisynaptic Schwann cells (PSCs), the synaptic glia of the neuromuscular junction (NMJ), suggesting that COL20A1 plays important roles in PSCs and at the NMJ. To investigate this possibility, we generated mice lacking Col20a1 only in Schwann cells (Col20a1-SCKO) and globally (Col20a1-gKO). PSCs and NMJs were morphologically unchanged in adult Col20a1-SCKO mice despite these conditional mice exhibiting gait abnormalities. Additional analysis revealed roles of COL20A1 at regenerating NMJs. We found that loss of COL20A1 altered the time course of migrating Schwann cells associated with NMJs. It also inhibited the remodeling of the post-synaptic region that naturally occurs following reinnervation. However, the timing of NMJ reinnervation was unchanged in Col20a1-SCKO compared to control mice. We next examined adult Col20a1-gKO mice. These mice did not exhibit overt morphological differences compared to control mice. Col20a1-gKO mice also did not exhibit NMJ alterations despite presenting with increased mass of the extensor digitorum longus and soleus muscles. Together, these data provide important leads about potential roles of COL20A1 in healthy and injured adult PSCs, NMJs, and muscles.
最近发现,XX型胶原蛋白α1(COL20A1)高度集中在突触周围施万细胞(PSC)中,这是神经肌肉接头(NMJ)的突触神经胶质细胞,表明COL20A1在PSC和NMJ中发挥重要作用。为了研究这种可能性,我们构建了仅在施万细胞中缺乏Col20a1的小鼠(Col20a1-SCKO)和全身缺乏Col20a1的小鼠(Col20a1-gKO)。尽管这些条件性小鼠表现出步态异常,但成年Col20a1-SCKO小鼠的PSC和NMJ在形态上没有变化。进一步分析揭示了COL20A1在再生NMJ中的作用。我们发现,COL20A1的缺失改变了与NMJ相关的施万细胞迁移的时间进程。它还抑制了再支配后自然发生的突触后区域重塑。然而,与对照小鼠相比,Col20a1-SCKO小鼠的NMJ再支配时间没有变化。接下来,我们检查了成年Col20a1-gKO小鼠。与对照小鼠相比,这些小鼠没有表现出明显的形态差异。尽管Col20a1-gKO小鼠的趾长伸肌和比目鱼肌质量增加,但它们也没有表现出NMJ改变。总之,这些数据为COL20A1在健康和受伤的成年PSC、NMJ和肌肉中的潜在作用提供了重要线索。