Department of Zoology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
Department of Zoology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada
J Neurosci. 2020 Apr 22;40(17):3360-3373. doi: 10.1523/JNEUROSCI.1397-19.2020. Epub 2020 Apr 7.
The nervous system is ensheathed by a layer of outer glial cells, the perineurial glia, and a specialized extracellular matrix, the neural lamella. The function of perineurial glial cells and how they interact with the extracellular matrix are just beginning to be elucidated. Integrin-based focal adhesion complexes link the glial membrane to the extracellular matrix, but little is known about integrin's regulators in the glia. The transmembrane Ig domain protein Basigin/CD147/EMMPRIN is highly expressed in the perineurial glia surrounding the larval nervous system. Here we show that Basigin associates with integrin at the focal adhesions to uphold the structure of the glia-extracellular matrix sheath. Knockdown of Basigin in perineurial glia using RNAi results in significant shortening of the ventral nerve cord, compression of the glia and extracellular matrix in the peripheral nerves, and reduction in larval locomotion. We determined that Basigin is expressed in close proximity to integrin at the glial membrane, and that expression of the extracellular integrin-binding domain of Basigin is sufficient to rescue peripheral glial compression. We also found that a reduction in expression of integrin at the membrane rescues the ventral nerve cord shortening, peripheral glial compression, and locomotor phenotypes, and that reduction in the integrin-binding protein Talin can partially rescue glial compression. These results identify Basigin as a potential negative regulator of integrin in the glia, supporting proper glial and extracellular matrix ensheathment of the nervous system. The glial cells and extracellular matrix play important roles in supporting and protecting the nervous system, but the interactions between these components have not been well characterized. Our study identified expression of a conserved Ig superfamily protein, Basigin, at the glial membrane of where it associates with the integrin-based focal adhesion complexes to ensure proper ensheathment of the CNS and PNS. Loss of Basigin in the glia results in an overall compression of the nervous system due to integrin dysregulation, which causes locomotor defects in the animals. This underlies the importance of glia-matrix communication for structural and functional support of the nervous system.
神经系统被一层外胶质细胞、神经外膜胶质和特殊的细胞外基质——神经板所包裹。神经外膜胶质细胞的功能以及它们与细胞外基质的相互作用才刚刚开始被阐明。整合素基的粘着斑复合物将神经胶质膜与细胞外基质连接起来，但对于整合素在神经胶质中的调节因子知之甚少。跨膜 Ig 结构域蛋白 Basigin/CD147/EMMPRIN 在幼虫神经系统周围的神经外膜胶质细胞中高度表达。在这里，我们发现 Basigin 在粘着斑处与整合素结合，维持神经胶质细胞-细胞外基质鞘的结构。用 RNAi 敲低神经外膜胶质细胞中的 Basigin 会导致腹神经索显著缩短、外周神经中的神经胶质和细胞外基质压缩以及幼虫运动能力降低。我们确定 Basigin 在神经胶质膜上与整合素紧密相邻表达，并且 Basigin 的细胞外整合素结合结构域的表达足以挽救外周神经胶质细胞的压缩。我们还发现，膜上整合素表达的减少可以挽救腹神经索缩短、外周神经胶质细胞压缩和运动表型，并且整合素结合蛋白 Talin 的减少可以部分挽救胶质细胞的压缩。这些结果表明 Basigin 是神经胶质中整合素的潜在负调节剂，支持神经系统的适当神经胶质和细胞外基质包裹。神经胶质细胞和细胞外基质在支持和保护神经系统方面发挥着重要作用，但这些成分之间的相互作用尚未得到很好的描述。我们的研究在神经胶质细胞膜上鉴定出一种保守的 Ig 超家族蛋白 Basigin 的表达，它与基于整合素的粘着斑复合物结合，以确保中枢神经系统和周围神经系统的适当包裹。神经胶质细胞中 Basigin 的缺失会导致整合素失调，从而导致动物的运动缺陷，从而导致整个神经系统的压缩。这突显了神经胶质-基质通讯对于神经系统结构和功能支持的重要性。
