Proteoglycans (PGs) in the extracellular matrix (ECM) play vital roles in axon growth and navigation, plasticity, and regeneration of injured neurons. Different classes of PGs may support or inhibit cell growth, and their functions are determined in part by highly specific structural features. Among these, the pattern of sulfation on the PG sugar chains is a paramount determinant of a diverse and flexible set of outcomes. Recent studies of PG sulfation illustrate the challenges of attributing biological actions to specific sulfation patterns, and suggest ways in which highly similar molecules may exert opposing effects on neurons. The receptors for PGs, which have yet to be fully characterized, display a similarly nuanced spectrum of effects. Different classes of PG function via overlapping families of receptors and signaling pathways. This enables them to control axon growth and guidance with remarkable specificity, but it poses challenges for determining the precise binding interactions and downstream effects of different PGs and their assorted sulfated epitopes. This review examines existing and emerging evidence for the roles of PG sulfation and receptor interactions in determining how these complex molecules influence neuronal development, growth, and function.

中文翻译：

---

蛋白多糖硫酸化和受体信号转导的灵活作用

细胞外基质 (ECM) 中的蛋白多糖 (PG) 在轴突生长和导航、可塑性和受损神经元再生中起着至关重要的作用。不同类别的 PG 可能支持或抑制细胞生长，它们的功能部分取决于高度特异性的结构特征。其中，PG 糖链上的硫酸化模式是多样化和灵活结果集的重要决定因素。最近对 PG 硫酸化的研究说明了将生物作用归因于特定硫酸化模式的挑战，并提出了高度相似的分子可能对神经元发挥相​​反作用的方式。尚未完全表征的 PG 受体显示出类似的细微影响范围。不同类别的 PG 通过重叠的受体家族和信号通路发挥作用。这使它们能够以显着的特异性控制轴突生长和引导，但它对确定不同 PG 及其各种硫酸化表位的精确结合相互作用和下游效应提出了挑战。本综述检查了现有和新出现的证据，证明 PG 硫酸化和受体相互作用在确定这些复杂分子如何影响神经元发育、生长和功能方面的作用。