Tomaselli K J, Reichardt L F, Bixby J L
J Cell Biol. 1986 Dec;103(6 Pt 2):2659-72. doi: 10.1083/jcb.103.6.2659.
We have compared neurite outgrowth on extracellular matrix (ECM) constituents to outgrowth on glial and muscle cell surfaces. Embryonic chick ciliary ganglion (CG) neurons regenerate neurites rapidly on surfaces coated with laminin (LN), fibronectin (FN), conditioned media (CM) from several non-neuronal cell types that secrete LN, and on intact extracellular matrices. Neurite outgrowth on all of these substrates is blocked by two monoclonal antibodies, CSAT and JG22, that prevent the adhesion of many cells, including neurons, to the ECM constituents LN, FN, and collagen. Neurite outgrowth is inhibited even on mixed LN/poly-D-lysine substrates where neuronal attachment is independent of LN. Therefore, neuronal process outgrowth on extracellular matrices requires the function of neuronal cell surface molecules recognized by these antibodies. The surfaces of cultured astrocytes, Schwann cells, and skeletal myotubes also promote rapid process outgrowth from CG neurons. Neurite outgrowth on these surfaces, though, is not prevented by CSAT or JG22 antibodies. In addition, antibodies to a LN/proteoglycan complex that block neurite outgrowth on several LN-containing CM factors and on an ECM extract failed to inhibit cell surface-stimulated neurite outgrowth. After extraction with a nonionic detergent, Schwann cells and myotubes continue to support rapid neurite outgrowth. However, the activity associated with the detergent insoluble residue is blocked by CSAT and JG22 antibodies. Detergent extraction of astrocytes, in contrast, removes all neurite-promoting activity. These results provide evidence for at least two types of neuronal interactions with cells that promote neurite outgrowth. One involves adhesive proteins present in the ECM and ECM receptors on neurons. The second is mediated through detergent-extractable macromolecules present on non-neuronal cell surfaces and different, uncharacterized receptor(s) on neurons. Schwann cells and skeletal myotubes appear to promote neurite outgrowth by both mechanisms.
我们将细胞外基质（ECM）成分上的神经突生长与神经胶质细胞和肌肉细胞表面的神经突生长进行了比较。胚胎鸡睫状神经节（CG）神经元在涂有层粘连蛋白（LN）、纤连蛋白（FN）、几种分泌LN的非神经元细胞类型的条件培养基（CM）以及完整细胞外基质的表面上能迅速再生神经突。所有这些底物上的神经突生长都被两种单克隆抗体CSAT和JG22所阻断，这两种抗体可阻止包括神经元在内的许多细胞与ECM成分LN、FN和胶原蛋白的粘附。即使在神经元附着独立于LN的混合LN/聚-D-赖氨酸底物上，神经突生长也会受到抑制。因此，细胞外基质上的神经元突起生长需要这些抗体识别的神经元细胞表面分子的功能。培养的星形胶质细胞、雪旺细胞和骨骼肌管的表面也能促进CG神经元快速长出突起。然而，CSAT或JG22抗体并不能阻止这些表面上的神经突生长。此外，针对LN/蛋白聚糖复合物的抗体，可阻断几种含LN的CM因子和ECM提取物上的神经突生长，但未能抑制细胞表面刺激的神经突生长。用非离子去污剂提取后，雪旺细胞和骨骼肌管仍能支持神经突快速生长。然而，与去污剂不溶性残渣相关的活性被CSAT和JG22抗体所阻断。相比之下，去污剂提取星形胶质细胞会消除所有促进神经突生长的活性。这些结果为至少两种促进神经突生长的神经元与细胞间相互作用提供了证据。一种涉及ECM中存在的粘附蛋白和神经元上的ECM受体。第二种是通过非神经元细胞表面存在的可被去污剂提取的大分子以及神经元上不同的、未鉴定的受体介导的。雪旺细胞和骨骼肌管似乎通过这两种机制促进神经突生长。
