F. M. Kirby Neurobiology Center, Children's Hospital Boston, Boston, Massachusetts, United States of America.
PLoS One. 2010 Dec 6;5(12):e15223. doi: 10.1371/journal.pone.0015223.
Nuclear import is required for communication between the cytoplasm and the nucleus and to enact lasting changes in gene transcription following stimuli. Binding to an Importin-α molecule in the cytoplasm is often required to mediate nuclear entry of a signaling protein. As multiple isoforms of Importin-α exist, some may be responsible for the entry of distinct cargoes rather than general nuclear import. Indeed, in neuronal systems, Importin-α isoforms can mediate very specific processes such as axonal tiling and communication of an injury signal. To study nuclear import during development, we examined the expression and function of Importin-α2 in Drosophila melanogaster. We found that Importin-α2 was expressed in the nervous system where it was required for normal active zone density at the NMJ and axonal commissure formation in the central nervous system. Other aspects of synaptic morphology at the NMJ and the localization of other synaptic markers appeared normal in importin-α2 mutants. Importin-α2 also functioned in development of the body wall musculature. Mutants in importin-α2 exhibited errors in muscle patterning and organization that could be alleviated by restoring muscle expression of Importin-α2. Thus, Importin-α2 is needed for some processes in the development of both the nervous system and the larval musculature.
核输入对于细胞质和细胞核之间的通讯以及在刺激后对基因转录进行持久改变是必需的。与细胞质中的 Importin-α 分子结合通常是介导信号蛋白进入细胞核所必需的。由于存在多种 Importin-α 异构体,其中一些可能负责特定货物的进入,而不是一般的核输入。事实上,在神经元系统中,Importin-α 异构体可以介导非常特定的过程,如轴突平铺和损伤信号的传递。为了在发育过程中研究核输入,我们在果蝇中研究了 Importin-α2 的表达和功能。我们发现 Importin-α2 在神经系统中表达,它对于 NMJ 处正常的活性区密度和中枢神经系统中轴突连接形成是必需的。在 Importin-α2 突变体中,NMJ 处的其他突触形态和其他突触标记物的定位的其他方面似乎正常。Importin-α2 也在体壁肌肉发育中发挥作用。Importin-α2 突变体表现出肌肉模式和组织的错误,通过恢复 Importin-α2 在肌肉中的表达可以缓解这些错误。因此,Importin-α2 对于神经系统和幼虫肌肉组织的发育中的某些过程是必需的。