Antennapedia homeobox peptide regulates neural morphogenesis.
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.
Joliot
A
A
Centre National de la Recherche Scientifique URA 1414, Département de Biologie, Ecole Normale Supérieure, Paris, France.
Pernelle
C
C
Deagostini-Bazin
H
H
Prochiantz
A
A
D000818:Animals; D051943:Antennapedia Homeodomain Protein; D001483:Base Sequence; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins; D004625:Embryo, Nonmammalian / Q000502:physiology; D005801:Genes, Homeobox; D018398:Homeodomain Proteins; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009420:Nervous System / Q000166:cytology / Q000196:embryology; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D014157:Transcription Factors
D051943:Antennapedia Homeodomain Protein; C497974:Antp protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D014157:Transcription Factors