Neurotrophic activity of a homeobox peptide.

Homeoproteins are well known for their role in defining the shape of organs during early development. The late expression of some homeogenes in the nervous system suggests that they might have other, additional functions, possibly in neurite growth and target recognition. The 60 amino acid-long peptide corresponding to the homeobox of Antennapedia (pAntp) translocates through the membrane of neurons in culture and reaches their nuclei. This process is followed by an enhanced morphological differentiation of the neurons. Internalization by neurons is four-fold that observed with fibroplasts. This difference is abolished upon treatment with Endo-N which specifically cleaves alpha,2-8 bonds in polysialic acid. To understand the mode of action of the peptide, we constructed three mutants modified in their capacity to specifically bind promoters and/or to translocate through the cell membrane. The biological properties of the mutants demonstrate that the neurotrophic action of pAntp requires its internalization and integrity of its specific DNA-binding capacity.