ANTENNAPEDIA HOMEOBOX PEPTIDE REGULATES NEURAL MORPHOGENESIS

ANTENNAPEDIA HOMEOBOX PEPTIDE REGULATES NEURAL MORPHOGENESIS
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DOI:
10.1073/pnas.88.5.1864
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发表时间:
1991-03-01
影响因子:
11.1
通讯作者:
PROCHIANTZ, A
PROCHIANTZ, A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
JOLIOT, A;PERNELLE, C;PROCHIANTZ, A

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我们合成了与果蝇触须基因同源盒序列相对应的60个氨基酸的多肽。该肽(pAntp)识别了与Hox-1.3启动子区域结合的共识基序。将pAntp机械导入哺乳动物神经细胞后,神经元培养物发生了显著的形态分化。此外,将pAntp直接添加到已经分化的神经元培养物中,穿透细胞,进一步增强其形态分化。在经典和共聚焦荧光显微镜下检查活的和固定的神经元表明,pAntp在神经细胞的所有区域都被捕获,并在细胞核中积累。此外,在蛋白质合成抑制剂环己亚胺的存在下,pAntp对神经突延伸的作用被阻断。因此,我们的研究结果表明,神经元对天线基同源盒肽具有有效的摄取系统,并表明pAntp与神经细胞核中存在的共识基序的结合影响了神经元的形态发生程序。
We synthesized the 60-amino acid polypeptide corresponding to the sequence of the Drosophila antennapedia gene homeobox. This peptide (pAntp) recognized the consensus motif for binding to the promoter region of Hox-1.3. pAntp mechanically introduced into mammalian nerve cells provoked a dramatic morphological differentiation of the neuronal cultures. Moreover, pAntp directly added to already differentiated neuronal cultures penetrated the cells and further augmented their morphological differentiation. Examination of live and fixed neurons in classical and confocal fluorescence microscopy demonstrated that pAntp was captured at all regions of the nerve cells and accumulated in the nuclei. In addition, the effect of pAntp on neurite extension was blocked in the presence of the protein synthesis inhibitor cycloheximide. Thus, our results demonstrate that neurons possess an efficient uptake system for the antennapedia homeobox peptide and suggest that binding of pAntp to consensus motifs present in nerve cell nuclei influences neuronal morphogenetic programs.