Miller Gregory M, Hsieh-Wilson Linda C
Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125, USA.
Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125, USA.
Exp Neurol. 2015 Dec;274(Pt B):115-25. doi: 10.1016/j.expneurol.2015.08.015. Epub 2015 Aug 24.
Chondroitin sulfate proteoglycans (CSPGs) play important roles in the developing and mature nervous system, where they guide axons, maintain stable connections, restrict synaptic plasticity, and prevent axon regeneration following CNS injury. The chondroitin sulfate glycosaminoglycan (CS GAG) chains that decorate CSPGs are essential for their functions. Through these sugar chains, CSPGs are able to bind and regulate the activity of a diverse range of proteins. CSPGs have been found both to promote and inhibit neuronal growth. They can promote neurite outgrowth by binding to various growth factors such as midkine (MK), pleiotrophin (PTN), brain-derived neurotrophic factor (BDNF) and other neurotrophin family members. CSPGs can also inhibit neuronal growth and limit plasticity by interacting with transmembrane receptors such as protein tyrosine phosphatase σ (PTPσ), leukocyte common antigen-related (LAR) receptor protein tyrosine phosphatase, and the Nogo receptors 1 and 3 (NgR1 and NgR3). These CS-protein interactions depend on specific sulfation patterns within the CS GAG chains, and accordingly, particular CS sulfation motifs are upregulated during development, in the mature nervous system, and in response to CNS injury. Thus, spatiotemporal regulation of CS GAG biosynthesis may provide an important mechanism to control the functions of CSPGs and to modulate intracellular signaling pathways. Here, we will discuss these sulfation-dependent processes and highlight how the CS sugars on CSPGs contribute to neuronal growth, axon guidance, and plasticity in the nervous system.
硫酸软骨素蛋白聚糖（CSPGs）在发育中的和成熟的神经系统中发挥着重要作用，它们引导轴突、维持稳定连接、限制突触可塑性，并在中枢神经系统损伤后阻止轴突再生。修饰CSPGs的硫酸软骨素糖胺聚糖（CS GAG）链对其功能至关重要。通过这些糖链，CSPGs能够结合并调节多种蛋白质的活性。已发现CSPGs既能促进也能抑制神经元生长。它们可以通过与各种生长因子如中期因子（MK）、多效蛋白（PTN）、脑源性神经营养因子（BDNF）和其他神经营养因子家族成员结合来促进神经突生长。CSPGs还可以通过与跨膜受体如蛋白酪氨酸磷酸酶σ（PTPσ）、白细胞共同抗原相关（LAR）受体蛋白酪氨酸磷酸酶以及Nogo受体1和3（NgR1和NgR3）相互作用来抑制神经元生长并限制可塑性。这些CS-蛋白质相互作用取决于CS GAG链内的特定硫酸化模式，因此，特定的CS硫酸化基序在发育过程中、成熟神经系统中以及对中枢神经系统损伤的反应中会上调。因此，CS GAG生物合成的时空调节可能提供一种重要机制来控制CSPGs的功能并调节细胞内信号通路。在这里，我们将讨论这些依赖硫酸化的过程，并强调CSPGs上的CS糖如何促进神经系统中的神经元生长、轴突导向和可塑性。
