Perry Rotem Ben-Tov, Fainzilber Mike
Dept. of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Semin Cell Dev Biol. 2009 Jul;20(5):600-6. doi: 10.1016/j.semcdb.2009.04.014. Epub 2009 May 4.
Active nucleocytoplasmic transport of macromolecules requires soluble transport carriers of the importin/karyopherin superfamily. Although the nuclear transport machinery is essential in all eukaryotic cells, neurons must also mobilise importins and associated proteins to overcome unique spatiotemporal challenges. These include switches in importin alpha subtype expression during neuronal differentiation, localized axonal synthesis of importin beta1 to coordinate a retrograde injury signaling complex on axonal dynein, and trafficking of regulatory and signaling molecules from synaptic terminals to cell bodies. Targeting of RNAs encoding critical components of the importins complex and the Ran system to axons allows sophisticated local regulation of the system for mobilization upon need. Finally, a number of importin family members have been associated with mental or neurodegenerative diseases. The extended roles recently discovered for importins in the nervous system might also be relevant in non-neuronal cells, and the localized modes of importin regulation in neurons offer new avenues to interrogate their cytoplasmic functions.
大分子的主动核质运输需要输入蛋白/核转运蛋白超家族的可溶性运输载体。尽管核运输机制在所有真核细胞中都是必不可少的，但神经元还必须调动输入蛋白和相关蛋白来克服独特的时空挑战。这些挑战包括神经元分化过程中输入蛋白α亚型表达的转变、输入蛋白β1在轴突局部合成以协调轴突动力蛋白上的逆行损伤信号复合物，以及调节和信号分子从突触末端向细胞体的运输。将编码输入蛋白复合物和Ran系统关键成分的RNA靶向轴突，可以对该系统进行精细的局部调节，以便在需要时进行动员。最后，一些输入蛋白家族成员与精神疾病或神经退行性疾病有关。最近在神经系统中发现的输入蛋白的扩展作用可能在非神经元细胞中也具有相关性，并且神经元中输入蛋白调节的局部模式为研究其细胞质功能提供了新途径。
