Griffith Institute for Drug Discovery, 170 Kessels Rd, Griffith University, Nathan, 4111, Queensland, Australia; Clem Jones Centre for Neurobiology and Stem Cell Research, 170 Kessels Rd, Griffith University, Brisbane, 4111, QLD, Australia.
Griffith Institute for Drug Discovery, 170 Kessels Rd, Griffith University, Nathan, 4111, Queensland, Australia; Clem Jones Centre for Neurobiology and Stem Cell Research, 170 Kessels Rd, Griffith University, Brisbane, 4111, QLD, Australia; Menzies Health Institute Queensland, Parklands Drive, Griffith University, Southport, 4222, QLD, Australia.
Mol Cell Neurosci. 2018 Apr;88:189-200. doi: 10.1016/j.mcn.2018.01.001. Epub 2018 Jan 11.
Lamellipodia in Schwann cells (SCs) are crucial for myelination, but their other biological functions remain largely uncharacterised. Two types of lamellipodia exist in SCs: axial lamellipodia at the outermost edge of the cell processes, and radial lamellipodia appearing peripherally along the entire cell. We have previously shown that radial lamellipodia on olfactory glia (olfactory ensheathing cells; OECs) promote cell-cell adhesion, contact-mediated migration and phagocytosis. Here we have investigated whether lamellipodia in SCs have similar roles. Using live-cell imaging, we show that the radial lamellipodia in SCs are highly motile, appear at multiple cellular sites and rapidly move in a wave-like manner. We found that axial and radial lamellipodia had strikingly different roles and are regulated by different intracellular pathways. Axial lamellipodia initiated interactions with other SCs and with neurons by contacting radial lamellipodia on SCs, and budding neurites/axons. Most SC-SC interactions resulted in repulsion, and, lamellipodial activity (unlike in OECs) did not promote contact-mediated migration. We show that lamellipodia are crucial for SC-mediated phagocytosis of both axonal debris and bacteria, and demonstrated that inhibition of lamellipodial activity by blocking the Rho/Rac pathways also inhibits phagocytosis. We also show that heregulin, which induces SC differentiation and maturation, alters lamellipodial behaviour but does not affect phagocytic activity. Overall, the results show that SC lamellipodia are important for cell interactions and phagocytosis.
施旺细胞（SCs）中的片状伪足对于髓鞘形成至关重要，但它们的其他生物学功能仍在很大程度上未被阐明。SCs 中有两种类型的片状伪足：位于细胞突起最外缘的轴向片状伪足，以及沿整个细胞外周出现的径向片状伪足。我们之前已经表明，嗅神经胶质细胞（嗅鞘细胞；OEC）上的径向片状伪足可促进细胞-细胞黏附、接触介导的迁移和吞噬作用。在这里，我们研究了 SC 中的片状伪足是否具有类似的作用。通过活细胞成像，我们显示 SC 中的径向片状伪足具有高度的运动性，出现在多个细胞部位，并以波状方式快速移动。我们发现，轴向和径向片状伪足具有明显不同的作用，并且受到不同的细胞内途径调节。轴向片状伪足通过接触 SC 上的径向片状伪足与其他 SC 和神经元发起相互作用，并萌芽神经突/轴突。大多数 SC-SC 相互作用导致排斥，并且，与 OEC 不同，片状伪足活性不促进接触介导的迁移。我们表明片状伪足对于 SC 介导的对轴突碎片和细菌的吞噬作用至关重要，并且证明通过阻断 Rho/Rac 途径抑制片状伪足活性也抑制了吞噬作用。我们还表明，表皮生长因子（HRG）诱导 SC 分化和成熟，改变了片状伪足的行为，但不影响吞噬活性。总的来说，这些结果表明 SC 片状伪足对于细胞相互作用和吞噬作用很重要。
