Details

Autor(en) / Beteiligte

• Isabelle Le Roux
• Alain Henri Joliot
• Evelyne Bloch-Gallego
• Alain Prochiantz
• Michael Volovitch

Titel

Neurotrophic Activity of the Antennapedia Homeodonian Depends on Its Specific DNA-Binding Properties

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1993-10, Vol.90 (19), p.9120-9124

Ort / Verlag

National Academy of Sciences of the United States of America

Erscheinungsjahr

1993

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• In previous reports we have demonstrated that the 60-aa peptide corresponding to the homeodomain of the Drosophila protein Antennapedia (pAntp) translocates through the membrane of neurons in culture, accumulates in neuronal nuclei, and promotes neurite growth. To analyze the importance of specific pAntp DNA-binding properties in this phenomenon we have constructed three mutant versions of pAntp that differ in their ability to translocate through the membrane and to bind specifically the cognate sequence for homeodomains present in the promoter of HoxA5. We demonstrate that removing two hydrophobic residues of the third helix inhibits pAntp internalization and suppresses its neurotrophic activity. We also show that pAntp neurotrophic activity is lost when mutations are introduced in positions preserving its penetration and nuclear accumulation but abolishing its capacity to bind specifically the cognate DNA-binding motif for homeoproteins. Our results strongly suggest that pAntp neurotrophicity requires both its internalization and its specific binding to homeobox cognate sequences. We propose that homeoproteins might regulate important events in the morphological differentiation of the postmitotic neuron.