NEUROTROPHIC ACTIVITY OF AN HOMEOBOX PEPTIDE

The sixty aminoacid-long peptide corresponding to the homeobox of Ante nnapedia (pAntp) translocates through the membrane of neurons in cultu re and reaches their nuclei. This process is followed by an enhanced m orphological differentiation of the neurons. Internalization by neuron s is 4-fold that observed with fibroblasts. This difference is abolish ed upon treatment with Endo-N which specifically cleaves alpha, 2-8 bo unds in polysialic acid (PSA). To understand the mode of action of the peptide, the authors constructed three mutants modified in their capa city to specifically bind promoters and/or to translocate through the cell membrane. The biological properties of the mutants demonstrate th at the neurotrophic action of pAntp requires its internalization and t he integrity of its specific DNA-binding capacity.