TRANSCRIPTION FACTOR HOXA-5 IS TAKEN UP BY CELLS IN CULTURE AND CONVEYED TO THEIR NUCLEI

Homeoproteins are transcription factors known to be involved in the ea rly patterning of the nervous system and in lineage decisions. While s tudying a possible role for homeoproteins at later stages of neuronal differentiation, we observed that the Antennapedia homeodomain is inte rnalized by neurons, translocated to their nuclei, and enhances neurit e outgrowth. Studies with mutant homeodomains showed that neurite elon gation by post-mitotic vertebrate neurons is regulated by homeoprotein s. An intriguing possibility suggested by these results, is that full length homeoproteins might be able to translocate through neuronal mem branes. We now report that the entire Hoxa-5 homeoprotein is taken up by fibroblasts and neurons in culture and conveyed to their nuclei. In ternalization occurs at 4 and 37 degrees C, and at concentrations as l ow as 10 pM compatible with a physiological mechanism.