Goslin K, Schreyer D J, Skene J H, Banker G
Department of Anatomy, Cell Biology, and Neurobiology, Albany Medical College, New York 12208.
J Neurosci. 1990 Feb;10(2):588-602. doi: 10.1523/JNEUROSCI.10-02-00588.1990.
GAP-43, a neuron specific growth-associated protein, is selectively distributed to the axonal domain in developing neurons; it is absent from dendrites and their growth cones. Using immunofluorescence microscopy, we have further examined the distribution of GAP-43 during the development of hippocampal neurons in culture, in order to determine when this polarized distribution arises. Cultured hippocampal neurons initially extend several short processes which have the potential to become either axons or dendrites. At this stage, before the morphological expression of polarity, GAP-43 is concentrated in the growth cones of these processes but is distributed more or less equally among them. Polarity becomes established when one of these processes elongates to become the axon. At the earliest stage when the emerging axon can be identified, GAP-43 is preferentially concentrated in its growth cone. During the next few days, as the remaining processes take on dendritic properties, they lose their residual GAP-43 immunoreactivity. Throughout development, GAP-43 remains highly concentrated in the axonal growth cone, but the concentration of GAP-43 in the axon shaft increases, beginning near the growth cone and progressing proximally until GAP-43 is uniformly distributed along the entire axon. At all stages of development, GAP-43 is also concentrated in the region of the Golgi apparatus. These results suggest that the selective sorting of at least one membrane protein into the axon coincides with the morphological expression of polarity. These results also raise the possibility that GAP-43 may play an important role in the early phases of axonal outgrowth, by which the functional polarity of neurons is established.
GAP - 43是一种神经元特异性生长相关蛋白,在发育中的神经元中选择性地分布于轴突区域;在树突及其生长锥中则不存在。我们利用免疫荧光显微镜进一步研究了培养的海马神经元发育过程中GAP - 43的分布情况,以确定这种极性分布何时出现。培养的海马神经元最初会伸出几个短突起,这些突起都有可能发育成轴突或树突。在这个阶段,即在极性形态表达之前,GAP - 43集中在这些突起的生长锥中,但在它们之间的分布大致相等。当其中一个突起伸长成为轴突时,极性就建立起来了。在能够识别出新生轴突的最早阶段,GAP - 43优先集中在其生长锥中。在接下来的几天里,随着其余突起呈现出树突特性,它们失去了残留的GAP - 43免疫反应性。在整个发育过程中,GAP - 43一直高度集中在轴突生长锥中,但轴突干中GAP - 43的浓度会增加,从生长锥附近开始并向近端发展,直到GAP - 43沿整个轴突均匀分布。在发育的所有阶段,GAP - 43也集中在高尔基体区域。这些结果表明,至少一种膜蛋白向轴突的选择性分选与极性的形态表达同时发生。这些结果还提出了一种可能性,即GAP - 43可能在轴突生长的早期阶段发挥重要作用,通过这一阶段建立神经元的功能极性。