Hunter James Kelly Research Institute, University at Buffalo, Buffalo, New York, USA.
Department of Biochemistry, University at Buffalo, Buffalo, New York, USA.
Glia. 2021 Jan;69(1):91-108. doi: 10.1002/glia.23886. Epub 2020 Aug 3.
In the developing peripheral nervous system, Schwann cells (SCs) extend their processes to contact, sort, and myelinate axons. The mechanisms that contribute to the interaction between SCs and axons are just beginning to be elucidated. Using a SC-neuron coculture system, we demonstrate that Arg-Gly-Asp (RGD) peptides that inhibit α -containing integrins delay the extension of SCs elongating on axons. α integrins in SC localize to sites of contact with axons and are expressed early in development during radial sorting and myelination. Short interfering RNA-mediated knockdown of the α integrin subunit also delays SC extension along axons in vitro, suggesting that α -containing integrins participate in axo-glial interactions. However, mice lacking the α subunit in SCs, alone or in combination with the potentially compensating α subunit, or the α partners β or β , myelinate normally during development and remyelinate normally after nerve crush, indicating that overlapping or compensatory mechanisms may hide the in vivo role of RGD-binding integrins.
在发育中的周围神经系统中,施万细胞(SCs)伸出其突起与轴突接触、分拣并髓鞘化。有助于SCs 和轴突相互作用的机制才刚刚开始被阐明。我们利用 SC-神经元共培养系统证实,抑制含 α 整合素的 Arg-Gly-Asp(RGD)肽延迟了 SC 沿轴突延伸的过程。SCs 中的 α 整合素定位于与轴突接触的部位,在发育过程中,沿放射状分拣和髓鞘化的早期阶段表达。α 整合素亚基的短干扰 RNA 介导的敲低也会延迟 SC 在体外沿轴突的延伸,表明含 α 的整合素参与了轴突-胶质细胞的相互作用。然而,SCs 中缺乏 α 亚基的小鼠,无论是单独缺乏还是与潜在的补偿性 α 亚基一起缺乏,或者缺乏 α 伴侣β 或β ,在发育过程中仍能正常髓鞘化,在神经挤压后也能正常进行髓鞘修复,这表明重叠或补偿机制可能掩盖了体内 RGD 结合整合素的作用。