Gordon-Weeks Phillip R
MRC Centre for Developmental Neurobiology, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.
Adv Exp Med Biol. 2017;1006:49-60. doi: 10.1007/978-4-431-56550-5_4.
Neuritogenesis is an early event in neuronal development in which newborn neurons first form growth cones, as a prerequisite for the formation of axons and dendrites. Growth cones emerge from segmented regions of the lamellipodium of embryonic neurons and grow away from the cell body leaving behind a neurite that will eventually polarise into an axon or dendrite. Growth cones also function to navigate precise routes through the embryo to locate an appropriate synaptic partner. Dynamic interactions between two components of the neuronal cytoskeleton, actin filaments and microtubules, are known to be essential for growth cone formation and hence neuritogenesis. The molecular mechanisms that coordinate interactions between actin filaments and dynamic microtubules during neuritogenesis are beginning to be understood. One candidate pathway coupling actin filaments to microtubules consists of the actin filament-binding protein drebrin and the microtubule-binding +TIP protein EB3. This pathway is regulated proximally by cyclin-dependent kinase 5 phosphorylation of drebrin but the upstream elements in the pathway have yet to be identified.
神经突发生是神经元发育过程中的早期事件,在此过程中,新生神经元首先形成生长锥,这是轴突和树突形成的前提条件。生长锥从胚胎神经元板状伪足的分段区域出现,并从细胞体生长离开,留下最终会极化成为轴突或树突的神经突。生长锥还起到引导精确路径穿过胚胎以找到合适突触伙伴的作用。已知神经元细胞骨架的两个组成部分——肌动蛋白丝和微管之间的动态相互作用对于生长锥形成以及神经突发生至关重要。在神经突发生过程中协调肌动蛋白丝和动态微管之间相互作用的分子机制正开始被理解。一种将肌动蛋白丝与微管耦合的候选途径由肌动蛋白丝结合蛋白 drebrin 和微管结合 +TIP 蛋白 EB3 组成。该途径在近端受 drebrin 的细胞周期蛋白依赖性激酶 5 磷酸化调节,但该途径中的上游元件尚未确定。