Letourneau P C, Roche F K, Shattuck T A, Lemmon V, Takeichi M
Department of Cell Biology and Neuroanatomy, University of Minnesota, Minneapolis 55455.
J Neurobiol. 1991 Oct;22(7):707-20. doi: 10.1002/neu.480220706.
During embryogenesis, Schwann cells interact with axons and other Schwann cells, as they migrate, ensheath axons, and participate in organizing peripheral nervous tissues. The experiments reported here indicate that the calcium-dependent molecule, N-cadherin, mediates adhesion of Schwann cells to neurites and to other Schwann cells. Cell cultures from chick dorsal root ganglia and sciatic nerves were maintained in media containing either 2 mM Ca++ or 0.2 mM Ca++, a concentration that inactivates calcium-dependent cadherins. When the leading lamellae of Schwann cells encountered migrating growth cones in medium with 2 mM Ca++, they usually remained extended, and the growth cones often advanced onto the Schwann cell upper surface. In the low Ca++ medium, the frequency of withdrawal of the Schwann cell lamella after contact with a growth cone was much greater, and withdrawal was the most common reaction to growth cone contact in medium with 2 mM Ca++ and anti-N-cadherin. Similarly, when motile leading margins of two Schwann cells touched in normal Ca++ medium, they often formed stable areas of contact. N-cadherin and vinculin were co-concentrated at these contact sites between Schwann cells. However, in low Ca++ medium or in the presence of anti-N-cadherin, interacting Schwann cells usually pulled away from each other in a behavior reminiscent of contact inhibition between fibroblasts. In cultures of dissociated cells in normal media, Schwann cells frequently were aligned along neurites, and ultrastructural examination showed extensive close apposition between plasma membranes of neurites and Schwann cells. When dorsal root ganglia explants were cultured with normal Ca++, Schwann cells migrated away from the explants in close association with extending neurites. All these interactions were disrupted in media with 0.2 mM Ca++. Alignment of Schwann cells along neurites was infrequent, as were extended close apposition between axonal and Schwann cell plasma membranes. Finally, migration of Schwann cells from ganglionic explants was reduced by disruption of adhesive contact with neurites. The addition of antibodies against N-cadherin to medium with normal Ca++ levels had similar effects as lowering the Ca++ concentration, but antibodies against the neuronal adhesive molecule, L1, had no effects on interactions between Schwann cells and neurites.
在胚胎发育过程中，施万细胞在迁移、包裹轴突并参与外周神经组织构建时，会与轴突及其他施万细胞相互作用。本文报道的实验表明，钙依赖性分子N-钙黏着蛋白介导施万细胞与神经突以及其他施万细胞之间的黏附。将鸡背根神经节和坐骨神经的细胞培养物维持在含有2 mM Ca++或0.2 mM Ca++的培养基中，0.2 mM Ca++的浓度会使钙依赖性钙黏着蛋白失活。当施万细胞的前缘薄片在含有2 mM Ca++的培养基中遇到迁移的生长锥时，它们通常会保持伸展状态，生长锥常常会延伸到施万细胞的上表面。在低Ca++培养基中，施万细胞薄片与生长锥接触后撤回的频率要高得多，并且在含有2 mM Ca++和抗N-钙黏着蛋白的培养基中，撤回是对生长锥接触最常见的反应。同样，当两个施万细胞的活动前缘在正常Ca++培养基中接触时，它们常常会形成稳定的接触区域。N-钙黏着蛋白和纽蛋白在施万细胞之间的这些接触位点共聚集。然而，在低Ca++培养基中或存在抗N-钙黏着蛋白时，相互作用的施万细胞通常会彼此拉开，这种行为让人联想到成纤维细胞之间的接触抑制。在正常培养基中的解离细胞培养物中，施万细胞经常沿着神经突排列，超微结构检查显示神经突和施万细胞的质膜之间有广泛的紧密贴附。当背根神经节外植体在正常Ca++条件下培养时，施万细胞与延伸的神经突紧密相连并从外植体迁移离开。所有这些相互作用在含有0.2 mM Ca++的培养基中均被破坏。施万细胞沿神经突的排列很少见，轴突和施万细胞质膜之间的紧密贴附延伸也很少见。最后，施万细胞与神经突的黏附接触被破坏，导致神经节外植体中施万细胞的迁移减少。向正常Ca++水平的培养基中添加抗N-钙黏着蛋白抗体具有与降低Ca++浓度类似的效果，但抗神经元黏附分子L1的抗体对施万细胞与神经突之间的相互作用没有影响。
