Hanamura Kenji
Department of Neurobiology and Behavior, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
Adv Exp Med Biol. 2017;1006:141-155. doi: 10.1007/978-4-431-56550-5_9.
During development, production of neurons from neural stem cells, migration of neurons from their birthplace to their final location, and extension of neurites, axons, and dendrites are important for the formation of functional neuronal circuits. The actin cytoskeleton has major roles in the morphological development of neurons. In this chapter, we focused on the distribution and function of the actin-binding protein, drebrin, to elucidate the importance of drebrin-bound F-actin in neurons during early developmental stages of neurons in embryonic, postnatal, and adult brains. There are three major isoforms of drebrin in the chicken brain (E1, E2, and A) and two major isoforms in the mammalian brain (E and A). Among these drebrin isoforms, drebrin E1 and E2 in chicken and drebrin E in the mammalian brain are involved in these neuronal stages. In migrating neurons of the developing and adult brain, drebrin is localized at the base of filopodia of leading processes, to regulate neuronal migration. In axonal growth cones, drebrin is localized in the transitional zone to regulate axonal growth by inhibiting actomyosin interactions and mediating the interactions between F-actin and microtubules. For axonal collateral branching, drebrin is localized at axonal actin patches and the base of filopodia, to accelerate the transition from actin patches to filopodia and stabilize the filopodia.
在发育过程中,神经干细胞产生神经元、神经元从其诞生地迁移到最终位置以及神经突、轴突和树突的延伸,对于功能性神经元回路的形成至关重要。肌动蛋白细胞骨架在神经元的形态发育中起主要作用。在本章中,我们重点研究了肌动蛋白结合蛋白德雷布林(drebrin)的分布和功能,以阐明在胚胎、出生后和成年大脑中神经元早期发育阶段,与德雷布林结合的丝状肌动蛋白(F-actin)在神经元中的重要性。鸡脑中德雷布林有三种主要异构体(E1、E2和A),哺乳动物脑中则有两种主要异构体(E和A)。在这些德雷布林异构体中,鸡脑中的德雷布林E1和E2以及哺乳动物脑中的德雷布林E参与了这些神经元阶段。在发育中和成年大脑的迁移神经元中,德雷布林定位于领先突起丝状伪足的基部,以调节神经元迁移。在轴突生长锥中,德雷布林定位于过渡区,通过抑制肌动球蛋白相互作用并介导F-肌动蛋白和微管之间的相互作用来调节轴突生长。对于轴突侧支分支,德雷布林定位于轴突肌动蛋白斑和丝状伪足的基部,以加速从肌动蛋白斑到丝状伪足的转变并稳定丝状伪足。