Davis-Lunn Mathew, Goult Benjamin T, Andrews Melissa R
Faculty of Environmental and Life Sciences, University of Southampton, Southampton SO17 1BJ, UK.
School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK.
Biology (Basel). 2023 Jul 3;12(7):954. doi: 10.3390/biology12070954.
Integrin receptors are essential contributors to neurite outgrowth and axon elongation. Activated integrins engage components of the extracellular matrix, enabling the growth cone to form point contacts, which connect the extracellular substrate to dynamic intracellular protein complexes. These adhesion complexes facilitate efficient growth cone migration and neurite extension. Major signalling pathways mediated by the adhesion complex are instigated by focal adhesion kinase (FAK), whilst axonal guidance molecules present in vivo promote growth cone turning or retraction by local modulation of FAK activity. Activation of FAK is marked by phosphorylation following integrin engagement, and this activity is tightly regulated during neurite outgrowth. FAK inhibition slows neurite outgrowth by reducing point contact turnover; however, mutant FAK constructs with enhanced activity stimulate aberrant outgrowth. Importantly, FAK is a major structural component of maturing adhesion sites, which provide the platform for actin polymerisation to drive leading edge advance. In this review, we discuss the coordinated signalling of integrin receptors and FAK, as well as their role in regulating neurite outgrowth and axon elongation. We also discuss the importance of the integrin-FAK axis in vivo, as integrin expression and activation are key determinants of successful axon regeneration following injury.
整合素受体是神经突生长和轴突延长的重要促成因素。活化的整合素与细胞外基质的成分结合，使生长锥形成点接触，将细胞外基质与动态的细胞内蛋白质复合物连接起来。这些黏附复合物促进生长锥的有效迁移和神经突延伸。黏附复合物介导的主要信号通路由粘着斑激酶（FAK）启动，而体内存在的轴突导向分子通过局部调节FAK活性来促进生长锥转向或回缩。FAK的激活以整合素结合后的磷酸化为标志，并且在神经突生长过程中这种活性受到严格调控。FAK抑制通过减少点接触更新来减缓神经突生长；然而，具有增强活性的突变FAK构建体则刺激异常生长。重要的是，FAK是成熟黏附位点的主要结构成分，为肌动蛋白聚合提供平台以驱动前沿前进。在本综述中，我们讨论整合素受体和FAK的协同信号传导，以及它们在调节神经突生长和轴突延长中的作用。我们还讨论了整合素-FAK轴在体内的重要性，因为整合素的表达和激活是损伤后轴突成功再生的关键决定因素。
