Liu Guofa, Dwyer Trisha
Department of Biological Sciences, University of Toledo, Toledo, OH, 43606, USA,
Neurosci Bull. 2014 Aug;30(4):569-83. doi: 10.1007/s12264-014-1444-6. Epub 2014 Jun 26.
Precise modulation of the cytoskeleton is involved in a variety of cellular processes including cell division, migration, polarity, and adhesion. In developing post-mitotic neurons, extracellular guidance cues not only trigger signaling cascades that act at a distance to indirectly regulate microtubule distribution, and assembly and disassembly in the growth cone, but also directly modulate microtubule stability and dynamics through coupling of guidance receptors with microtubules to control growth-cone turning. Microtubule-associated proteins including classical microtubule-associated proteins and microtubule plus-end tracking proteins are required for modulating microtubule dynamics to influence growth-cone steering. Multiple key signaling components, such as calcium, small GTPases, glycogen synthase kinase-3β, and c-Jun N-terminal kinase, link upstream signal cascades to microtubule stability and dynamics in the growth cone to control axon outgrowth and projection. Understanding the functions and regulation of microtubule dynamics in the growth cone provides new insights into the molecular mechanisms of axon guidance.
细胞骨架的精确调控参与多种细胞过程,包括细胞分裂、迁移、极性和黏附。在发育中的有丝分裂后神经元中,细胞外导向线索不仅触发远距离作用的信号级联反应,间接调节生长锥中的微管分布、组装和拆卸,还通过导向受体与微管的耦合直接调节微管稳定性和动力学,以控制生长锥转向。包括经典微管相关蛋白和微管正端追踪蛋白在内的微管相关蛋白,对于调节微管动力学以影响生长锥转向是必需的。多种关键信号成分,如钙、小GTP酶、糖原合酶激酶-3β和c-Jun氨基末端激酶,将上游信号级联与生长锥中的微管稳定性和动力学联系起来,以控制轴突生长和投射。了解生长锥中微管动力学的功能和调控,为轴突导向的分子机制提供了新的见解。