Volovitch M, le Roux I, Joliot A H, Bloch-Gallego E, Prochiantz A
CNRS URA 1414, Ecole Normale Supérieure, Paris, France.
Perspect Dev Neurobiol. 1993;1(3):133-8.
To test whether homeoproteins can act as genetic regulators in the processes of neurite growth, branching, guidance, and connectivity, the 60 amino acid homeodomain of Antennapedia was introduced in embryonic neurons in primary culture. It was hoped that this homeopeptide would bind to specific promoters and thus behave as a competitive inhibitor of endogenous homeoproteins. The introduction of the homeodomain in the nerve cells was made easy by its unexpected capability to translocate through the membranes and to accumulate within the nuclei. The presence of the homeodomain within the cells correlated with an increase in neurite growth and branching. The absence of activity of mutant peptides, still internalized but unable to bind with high affinity to homeoprotein cognate binding sites, strongly suggested that endogenous homeoproteins modulate neurite outgrowth and branching. Moreover, the efficient internalization of the homeobox peptide by live cells in culture raises the possibility that, in addition to their well-established role as cell-autonomous transcription factors, some homeoproteins may also exert paracrine functions. We examine how these hypotheses could modify our current views on the establishment and plasticity of neuronal networks.
为了测试同源异形蛋白是否能在神经突生长、分支、导向和连接过程中作为基因调节因子发挥作用，将触角足蛋白的60个氨基酸的同源结构域导入原代培养的胚胎神经元中。人们希望这种同源肽能与特定启动子结合，从而作为内源性同源异形蛋白的竞争性抑制剂发挥作用。同源结构域意外地具有穿过细胞膜并在细胞核内积累的能力，这使得将其导入神经细胞变得容易。细胞内同源结构域的存在与神经突生长和分支的增加相关。突变肽仍能内化但无法与同源蛋白的同源结合位点高亲和力结合，其无活性强烈表明内源性同源异形蛋白调节神经突的生长和分支。此外，培养中的活细胞对同源框肽的有效内化增加了一种可能性，即除了作为细胞自主转录因子已确立的作用外，一些同源异形蛋白可能还发挥旁分泌功能。我们研究了这些假设如何改变我们目前对神经网络建立和可塑性的看法。
