Chernousov Michael A, Rothblum Katrina, Stahl Richard C, Evans Ann, Prentiss Lisa, Carey David J
Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania 17822-2601, USA.
J Neurosci. 2006 Jan 11;26(2):508-17. doi: 10.1523/JNEUROSCI.2544-05.2006.
Schwann cell myelination requires interactions with the extracellular matrix (ECM) mediated by cell surface receptors. Previously, we identified a type V collagen family member, alpha4(V) collagen, which is expressed by Schwann cells during peripheral nerve differentiation. This collagen binds with high affinity to heparan sulfate through a unique binding motif in the noncollagenous N-terminal domain (NTD). The principal alpha4(V) collagen-binding protein on the Schwann cell surface is the heparan sulfate proteoglycan glypican-1. We investigated the role of alpha4(V) collagen and glypican-1 in Schwann cell terminal differentiation in cultures of Schwann cells and dorsal root ganglion neurons. Small interfering RNA-mediated suppression of glypican-1 expression decreased binding of alpha4(V)-NTD to Schwann cells, adhesion and spreading of Schwann cells on alpha4(V)-NTD, and incorporation of alpha4(V) collagen into Schwann cell ECM. In cocultures, alpha4(V) collagen coassembles with laminin on the surface of polarized Schwann cells to form tube-like ECM structures that are sites of myelination. Suppression of glypican-1 or alpha4(V) collagen expression significantly inhibited myelination. These results demonstrate an important role for these proteins in peripheral nerve terminal differentiation.
施万细胞髓鞘形成需要通过细胞表面受体介导与细胞外基质（ECM）相互作用。此前，我们鉴定出一种V型胶原家族成员，α4（V）胶原，其在周围神经分化过程中由施万细胞表达。这种胶原通过非胶原N端结构域（NTD）中的独特结合基序与硫酸乙酰肝素高亲和力结合。施万细胞表面主要的α4（V）胶原结合蛋白是硫酸乙酰肝素蛋白聚糖磷脂酰肌醇蛋白聚糖-1。我们研究了α4（V）胶原和磷脂酰肌醇蛋白聚糖-1在施万细胞和背根神经节神经元培养物中施万细胞终末分化中的作用。小干扰RNA介导的磷脂酰肌醇蛋白聚糖-1表达抑制降低了α4（V）-NTD与施万细胞的结合、施万细胞在α4（V）-NTD上的黏附与铺展，以及α4（V）胶原掺入施万细胞ECM。在共培养中，α4（V）胶原与层粘连蛋白在极化施万细胞表面共同组装形成管状ECM结构，这些结构是髓鞘形成的部位。抑制磷脂酰肌醇蛋白聚糖-1或α4（V）胶原表达显著抑制髓鞘形成。这些结果证明了这些蛋白在周围神经终末分化中的重要作用。
